Replication Protein A Directs Loading of the DNA Damage Checkpoint Clamp to 5′-DNA Junctions
Open accessAbstract
The heterotrimeric checkpoint clamp comprises the Saccharomyces cerevisiae Rad17, Mec3, and Ddc1 subunits (Rad17/3/1, the 9-1-1 complex in humans). This DNA damage response factor is loaded onto DNA by the Rad24-RFC (replication factor C-like complex with Rad24) clamp loader and ATP. Although Rad24-RFC alone does not bind to naked partial double-stranded DNA, coating of the single strand with single-stranded DNA-binding protein RPA (replication protein A) causes binding of Rad24-RFC via interactions with RPA. However, RPA-mediated binding is abrogated when the DNA is coated with RPA containing a rpa1-K45E (rfa1-t11) mutation. These properties allowed us to determine the role of RPA in clamp-loading specificity. The Rad17/3/1 clamp is loaded with comparable efficiency onto naked primer/template DNA with either a 3'-junction or a 5'-junction. Remarkably, when the DNA was coated with RPA, loading of Rad17/3/1 at 3'-junctions was completely inhibited, thereby providing specificity to loading at 5'-junctions. However, Rad17/3/1 loaded at 5'-junctions can slide across double-stranded DNA to nearby 3'-junctions and thereby affect the activity of proteins that act at 3'-termini. These studies show a unique specificity of the checkpoint loader for 5'-junctions of RPA-coated DNA. The implications of this specificity for checkpoint function are discussed.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The PCNA-like 9-1-1 complex (Rad9-Rad1-Hus1) is recruited preferentially to the 5'-primed single-stranded/double-stranded DNA junction by RPA and the Rad17-RFC clamp loader.
“The PCNA-like clamp 9-1-1 complex (Rad9-Rad1-Hus1) is recruited preferentially to the 5′-primed ssDNA/dsDNA junction by RPA and the clamp loader Rad17-RFC complex [102–105].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [105]
Cites
Checkpoints: Controls That Ensure the Order of Cell Cycle Events
Hartwell, L. H., & Weinert, T. A. (1989) · Science · doi:10.1126/science.2683079 · Cited by 3,053 · see citing works
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Zou, L., & Elledge, S. J. (2003) · Science · doi:10.1126/science.1083430 · Cited by 2,693 · see citing works
Wold, M. S. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.61 · Cited by 1,445 · see citing works
Self-citationCrystal structure of the eukaryotic DNA polymerase processivity factor PCNA
Krishna, T. S. R., Kong, X., Gary, S. L., Burgers, P., & Kuriyan, J. (1994) · Cell · doi:10.1016/0092-8674(94)90014-0 · Cited by 902 · see citing works
Self-citationRecombinant replication protein A: expression, complex formation, and functional characterization
Henricksen, L. A., Umbricht, C. B., & Wold, M. S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)78100-9 · Cited by 597 · see citing works
Self-citationStructure of the single-stranded-DNA-binding domain of replication protein A bound to DNA
Bochkarev, A. V., Pfuetzner, R. A., Edwards, A. M., & Frappier, L. (1997) · Nature · doi:10.1038/385176a0 · Cited by 559 · see citing works
Replication protein A-mediated recruitment and activation of Rad17 complexes
Zou, L., Liu, D., & Elledge, S. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336100100 · Cited by 431 · see citing works
Ellison, V., & Stillman, B. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000033 · Cited by 363 · see citing works
The PCNA–RFC Families of DNA Clamps and Clamp Loaders
Majka, J., & Burgers, P. (2004) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(04)78006-x · Cited by 328 · see citing works
Self-citationStructure of the RPA trimerization core and its role in the multistep DNA‐binding mechanism of RPA
Bochkareva, E., Korolev, S., Lees-Miller, S., & Bochkarev, A. (2002) · EMBO Journal · doi:10.1093/emboj/21.7.1855 · Cited by 325 · see citing works
Bermudez, V. P., Lindsey-Boltz, L. A., Cesare, A. J., Maniwa, Y., Griffith, J. D., Hurwitz, J., & Sancar, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437927100 · Cited by 324 · see citing works
Sun, Z., Fay, D. S., Marini, F., Foiani, M., & Stern, D. F. (1996) · Genes & Development · doi:10.1101/gad.10.4.395 · Cited by 300 · see citing works
Pellicioli, A., Lee, S. E., Lucca, C., Foiani, M., & Haber, J. E. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00177-0 · Cited by 290 · see citing works
Yeast Rad17/Mec3/Ddc1: A sliding clamp for the DNA damage checkpoint
Majka, J., & Burgers, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437148100 · Cited by 255 · see citing works
Self-citationMultiple competition reactions for RPA order the assembly of the DNA polymerase δ holoenzyme
Yuzhakov, A., Kelman, Z., Hurwitz, J., & O’Donnell, M. E. (1999) · The EMBO Journal · doi:10.1093/emboj/18.21.6189 · Cited by 212 · see citing works
A novel Rad24 checkpoint protein complex closely related to replication factor C
Green, C., Erdjument‐Bromage, H., Tempst, P., & Lowndes, N. F. (2000) · Current Biology · doi:10.1016/s0960-9822(99)00263-8 · Cited by 208 · see citing works
Genetic Analysis of Yeast RPA1 Reveals Its Multiple Functions in DNA Metabolism
Umezu, K., Sugawara, N., Chen, C., Haber, J. E., & Kolodner, R. D. (1998) · Genetics · doi:10.1093/genetics/148.3.989 · Cited by 206 · see citing works
Lcd1p Recruits Mec1p to DNA Lesions In Vitro and In Vivo
Rouse, J. W., & Jackson, S. P. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00507-5 · Cited by 179 · see citing works
Checkpoint activation regulates mutagenic translesion synthesisPreprint
Kai, M., & Wang, T. S. ‐. (2003) · Genes & Development · doi:10.1101/gad.1043203 · Cited by 157 · see citing works
ATP Utilization by Yeast Replication Factor C
Gomes, X. V., & Burgers, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011631200 · Cited by 155 · see citing works
Self-citationPaulovich, A. G., Armour, C. D., & Hartwell, L. H. (1998) · Genetics · doi:10.1093/genetics/150.1.75 · Cited by 133 · see citing works
Replication Protein A-Directed Unloading of PCNA by the Ctf18 Cohesion Establishment Complex
Bylund, G., & Burgers, P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5445-5455.2005 · Cited by 130 · see citing works
Self-citationToueille, M. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh652 · Cited by 122 · see citing works
Kim, H., & Brill, S. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.11.3725-3737.2001 · Cited by 121 · see citing works
Sabbioneda, S., Minesinger, B. K., Giannattasio, M., Plevani, P., Muzi-Falconi, M., & Jinks-Robertson, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507638200 · Cited by 116 · see citing works
Physical and functional interactions between nucleotide excision repair and DNA damage checkpoint
Giannattasio, M., Lazzaro, F., Longhese, M. P., Plevani, P., & Muzi‐Falconi, M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600051 · Cited by 113 · see citing works
Molecular mechanism of PCNA-dependent base excision repair
Matsumoto, Y. (2001) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(01)68095-4 · Cited by 110 · see citing works
Gomes, X. V., Gary, S. L., & Burgers, P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14541 · Cited by 107 · see citing works
Self-citationATP-independent loading of the proliferating cell nuclear antigen requires DNA ends.
Burgers, P., & Yoder, B. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80673-5 · Cited by 106 · see citing works
Self-citationThe human Rad9–Rad1–Hus1 checkpoint complex stimulates flap endonuclease 1
Wang, W., Brandt, P., Rossi, M. L., Lindsey-Boltz, L., Podust, V., Fanning, E., Sancar, A., & Bambara, R. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407686101 · Cited by 98 · see citing works
Proliferating Cell Nuclear Antigen Promotes Translesion Synthesis by DNA Polymerase ζ
Garg, P., Stith, C. M. W., Majka, J., & Burgers, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500173200 · Cited by 93 · see citing works
Self-citationKantake, N., Sugiyama, T., Kolodner, R. D., & Kowalczykowski, S. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302995200 · Cited by 92 · see citing works
Sibenaller, Z. A., Sorensen, B. R., & Wold, M. S. (1998) · Biochemistry · doi:10.1021/bi981110+ · Cited by 76 · see citing works
Self-citationThe S-phase checkpoint and its regulation in Saccharomyces cerevisiae
Longhese, M. P., Clerici, M., & Lucchini, G. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.009 · Cited by 74 · see citing works
RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase δ
Fortune, J. M., Stith, C. M. W., Kissling, G. E., Burgers, P., & Kunkel, T. A. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl403 · Cited by 71 · see citing works
Self-citationATP Utilization by Yeast Replication Factor C
Gary, S. L., Gomes, X. V., & Burgers, P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011633200 · Cited by 67 · see citing works
Self-citationReplication Protein A Is Required for Meiotic Recombination in Saccharomyces cerevisiae
Soustelle, C., Vedel, M., Kolodner, R. D., & Nicolas, A. G. (2002) · Genetics · doi:10.1093/genetics/161.2.535 · Cited by 64 · see citing works
Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis
Kai, M., & Wang, T. S. ‐. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.010 · Cited by 61 · see citing works
Bae, K. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg422 · Cited by 58 · see citing works
Clerici, M., Baldo, V., Mantiero, D., Lottersberger, F., Lucchini, G., & Longhese, M. P. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.23.10126-10144.2004 · Cited by 41 · see citing works
Requirement for ATP by the DNA Damage Checkpoint Clamp Loader
Majka, J., Chung, B. Y., & Burgers, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400898200 · Cited by 40 · see citing works
Self-citationAllen, B. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.17.3877 · Cited by 32 · see citing works
Kobayashi, M., Figaroa, F., Meeuwenoord, N. J., Jansen, L. E. T., & Siegal, G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511090200 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
ATR: an essential regulator of genome integrity
Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798 · see citing works
“The presence of RPA is also crucial for this reaction and imparts specificity in loading, thereby creating a preference for the 5′ primer en”
Maréchal, A., & Zou, L. (2015) · Cell Research · doi:10.1038/cr.2014.147 · Cited by 465 · see citing works
Sørensen, C. S., & Syljuåsen, R. G. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr697 · Cited by 316 · see citing works
“It has been suggested that these ends may be the loading site for the 9-1-1 complex (40).”
BackgroundTranslesion DNA Synthesis and Mutagenesis in Eukaryotes
Sale, J. E. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012708 · Cited by 282 · see citing works
“Significantly, full activation of the ATR-dependent replication checkpoint requires downstream repriming and recruitment of the 9-1-1 checkpoint clamp to the 50 phosphorylated end of the resulting RPAcoated gap (Zou and Elledge 2003; Majka et al. 2006).”
BackgroundThe Rad9-Hus1-Rad1 Checkpoint Clamp Regulates Interaction of TopBP1 with ATR
Lee, J., Kumagai, A., & Dunphy, W. G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704635200 · Cited by 281 · see citing works
Common mechanisms of PIKK regulation
Lovejoy, C. A., & Cortez, D. (2009) · DNA Repair · doi:10.1016/j.dnarep.2009.04.006 · Cited by 277 · see citing works
“RPA directs the recruitment of the 9-1-1 complex to the 5′ primer ends, effectively placing the components of the checkpoint activating structure in close proximity [20,21].”
BackgroundThe ATR pathway: Fine-tuning the fork
PAULSEN, R., & Cimprich, K. A. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.02.015 · Cited by 256 · see citing works
The structural determinants of checkpoint activation
MacDougall, C. A., Byun, T. S., Van, C., Yee, M.-C., & Cimprich, K. A. (2007) · Genes & Development · doi:10.1101/gad.1522607 · Cited by 240 · see citing works
Yan, S., Sorrell, M., & Berman, Z. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1666-4 · Cited by 247 · see citing works
“Rad17-RFC complex [102–105].”
The checkpoint clamp activates Mec1 kinase during initiation of the DNA damage checkpoint
Majka, J., Niedziela-Majka, A., & Burgers, P. M. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.11.027 · Cited by 186 · see citing works
Self-citationReplication protein A: directing traffic at the intersection of replication and repair
Oakley, G. G. (2010) · Frontiers in bioscience · doi:10.2741/3652 · Cited by 180 · see citing works
“This interaction is completely abolished with the mutant rfa-t11 protein indicating that RPA17 also binds to the N-terminus of RPA1 (98).”
BackgroundOligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians
Flynn, R. L., & Zou, L. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.488216 · Cited by 178 · see citing works
“Unlike the wild-type RPA, the rfa1-t11 mutant is unable to interact with Ddc2 (yeast homolog of human ATRIP), and fails to recruit Ddc2 and Ddc1 (yeast homolog of human Rad9) to sites of DNA damage (Zou and Elledge, 2003; Zou et al., 2003; Lucca et al., 2004; Majka et al., 2006).”
BackgroundXu, X., Vaithiyalingam, S., Glick, G. G., Mordes, D. A., Chazin, W., & Cortez, D. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01079-08 · Cited by 166 · see citing works
“The presence of RPA is critical for this reaction and imparts specificity in loading, creating a preference for a 5 rather than a 3 primer end (18, 36).”
BackgroundDifferential Regulation of the Cellular Response to DNA Double-Strand Breaks in G1
Barlow, J. H., Lisby, M., & Rothstein, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.01.016 · Cited by 160 · see citing works
Makarova, А. V., & Burgers, P. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.02.012 · Cited by 150 · see citing works
Self-citationReconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling
Choi, J.-H., Lindsey‐Boltz, L. A., Kemp, M. G., Mason, A. C., Wold, M. S., & Sancar, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007856107 · Cited by 144 · see citing works
“Based on the experience we have gained from establishing an RPA-ssDNA-dependent system, we expect it should be possible to develop an in vitro system dependent on the 9-1-1 complex as well by careful titration of the multiple components of the reaction (ATR-ATRIP, TopBP1, Rad17-RFC/9-1-1 complex, RPA, Chk1, and DNA) a…”
BackgroundInfluentialSelf-citationLangerak, P., & Russell, P. R. (2011) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0070 · Cited by 139 · see citing works
Navadgi, V. M., & Burgers, P. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.10.014 · Cited by 131 · see citing works
“On the other hand, Rad24-RFC loads 9-1-1 specifically onto 50-primer/template junctions (Majka et al., 2006a).”
InfluentialSelf-citationSingle- and double-stranded DNA: building a trigger of ATR-mediated DNA damage response: Figure 1.Preprint
Zou, L. (2007) · Genes & Development · doi:10.1101/gad.1550307 · Cited by 128 · see citing works
“Indeed, at HO-induced DSBs in yeast, the formation of long stretches of ssDNA is needed for robust phosphorylation of Rad53, an effector kinase of Mec1 (Vaze et al. 2002).”
BackgroundResultInfluentialEukaryotic DNA damage checkpoint activation in response to double-strand breaks
Finn, K., Lowndes, N. F., & Grenon, M. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0875-3 · Cited by 127 · see citing works
“It is proposed that the 9-1-1 complex, which loads specifically onto 50 junctions [174, 175], signals replication stress on the lagging strand, while pol e and the leading strand factors Dpb11 and Sld2 detect replication perturbations on the leading strand, with both pathways independently leading to Mec1 activation […”
BackgroundDore, A. S., Kilkenny, M. L., Rzechorzek, N. J., & Pearl, L. H. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.04.027 · Cited by 125 · see citing works
“Loaded 9-1-1 interacts with the BRCT domain protein TopBP1, which binds the phosphorylated C-terminal tail of Rad9 (Delacroix et al., 2007) and thereby activates the checkpoint kinase ATR (Lee et al., 2007), itself tethered in the vicinity of the damaged DNA via interaction of its constitutive partner ATRIP, with RPA…”
BackgroundYeast DNA replication protein Dpb11 activates the Mec1/ATR checkpoint kinase
Navadgi-Patil, V. M., & Burgers, P. M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807435200 · Cited by 121 · see citing works
Self-citationChoreography of recombination proteins during the DNA damage response
Lisby, M., & Rothstein, R. J. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.04.007 · Cited by 118 · see citing works
“In addition, RPA also recruits the alternative DNA clamp loader RAD17-RFC, which loads the 9-1-1 complex (RAD9-HUS1-RAD1) onto DNA [102-105].”
BackgroundDpb11 coordinates Mec1 kinase activation with cell cycle‐regulated Rad9 recruitment
Pfander, B., & Diffley, J. F. X. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.345 · Cited by 113 · see citing works
“This solution as well as five 1:5 dilutions were spotted on plates without drugs and incubated for 2 days.”
BackgroundMethodInfluentialTopBP1 and DNA polymerase-α directly recruit the 9-1-1 complex to stalled DNA replication forks
Yan, S., & Michael, W. M. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200810185 · Cited by 107 · see citing works
Dealing with DNA damage: Relationships between checkpoint and repair pathways
Warmerdam, D. O., & Kanaar, R. (2009) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2009.12.001 · Cited by 113 · see citing works
Cellular Functions of Human RPA1
Haring, S. J., Mason, A. C., Binz, S. K., & Wold, M. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800881200 · Cited by 112 · see citing works
Self-citationSurvey of the year 2006 commercial optical biosensor literature
Rich, R. L., & Myszka, D. G. (2007) · Journal of Molecular Recognition · doi:10.1002/jmr.862 · Cited by 111 · see citing works
Kumar, S., & Burgers, P. (2013) · Genes & Development · doi:10.1101/gad.204750.112 · Cited by 107 · see citing works
Self-citationContinued primer synthesis at stalled replication forks contributes to checkpoint activation
Van, C., Yan, S., Michael, W. M., Waga, S., & Cimprich, K. A. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200909105 · Cited by 100 · see citing works
“The ssDNA–dsDNA junction is critical for the recruitment of the Rad9–Hus1–Rad1 (9-1-1) complex, a heterotrimeric clamp with structural homology to proliferating cell nuclear antigen (PCNA), which is the processivity factor for replicative polymerases (Bermudez et al., 2003; Ellison and Stillman, 2003; Zou et al., 2003…”
BackgroundInfluentialCaldwell, C. C., & Spies, M. (2020) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2020.1813070 · Cited by 100 · see citing works
Role of Cyclin B1 Levels in DNA Damage and DNA Damage-Induced Senescence
Nakayama, Y., & Yamaguchi, N. (2013) · International review of cytology · doi:10.1016/b978-0-12-407695-2.00007-x · Cited by 101 · see citing works
Separate domains of Rev1 mediate two modes of DNA damage bypass in mammalian cells
Jansen, J. G., Tsaalbi-Shtylik, A., Hendriks, G., Gali, H., Hendel, A., Johansson, F., Erixon, K., Livneh, Z., Mullenders, L. H. F., Haracska, L., et al. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00071-09 · Cited by 99 · see citing works
“The 9-1-1 clamp is recruited to stalled forks independently of PCNA (46) at 5 primer-template junctions in vitro (35, 36).”
BackgroundMasuda-Sasa, T., Polaczek, P., Peng, X. P., Chen, L., & Campbell, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802244200 · Cited by 98 · see citing works
Navadgi-Patil, V. M., & Burgers, P. M. (2009) · DNA Repair · doi:10.1016/j.dnarep.2009.03.011 · Cited by 93 · see citing works
Self-citationNoncanonical Role of the 9-1-1 Clamp in the Error-Free DNA Damage Tolerance Pathway
Karras, G. I., Fumasoni, M., Sienski, G., Vanoli, F., Branzei, D., & Jentsch, S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.11.016 · Cited by 89 · see citing works
“Whereas PCNA is loaded on the 30 ends of gapped DNA (e.g., at replication forks), 9-1-1 is recruited to the 50 ends (e.g., at damaged sites), where it serves as a sensor for checkpoint signaling (Ellison and Stillman, 2003; Majka et al., 2006; Sancar et al., 2004).”
BackgroundThe RFC Clamp Loader: Structure and Function
Yao, N. Y., & O’Donnell, M. (2012) · Subcellular Biochemistry · doi:10.1007/978-94-007-4572-8_14 · Cited by 90 · see citing works
Anticheckpoint pathways at telomeres in yeast
Ribeyre, C., & Shore, D. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2225 · Cited by 88 · see citing works
“Increased binding of Rad24 in the mutants may be a direct consequence of stronger RPA association, as RPA itself promotes Rad24 loadin”
BackgroundPhysiological Tolerance to ssDNA Enables Strand Uncoupling during DNA Replication
Ercilla, A., Benada, J., Gadi, S. A., Zonderland, G., Baldi, G., Somyajit, K., Ochs, F., Costanzo, V., Lukas, J., & Toledo, L. I. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.067 · Cited by 73 · see citing works
“This distinction has been a topic of discussion because active forks have a priori the same molecular requirements for ATR activation as a stalled fork, namely ssDNA (at the lagging strand) and a 50 end junction to recruit TOPBP1 and the 9-1-1 complex (MacDougall et al., 2007; Majka et al., 2006).”
BackgroundRPA Inhibition Increases Replication Stress and Suppresses Tumor Growth
Glanzer, J. G., Liu, S., Wang, L., Mosel, A., Peng, A., & Oakley, G. G. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0306 · Cited by 76 · see citing works
“HAMNO induces γ-H2AX staining in a cell-cycle specific manner DBD-F binds ATRIP, Rad9, Rad17 and Nbs1 thereby recruiting and stabilizing the proteins involved in ATR activation (11, 13, 15, 27, 28).”
Timing and spacing of ubiquitin‐dependent DNA damage bypass
Ulrich, H. D. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.05.028 · Cited by 73 · see citing works
Niu, W., Li, Z., Zhan, W., Iyer, V. R., & Marcotte, E. M. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000120 · Cited by 74 · see citing works
“is another gene involved in DNA replication whose overexpression leads to G2/M delay. The Rfa1p protein is a subunit of the heterotrimeric replication protein A (RPA), which is involved in DNA replication, repair, and the DNA damage checkpoint”
BackgroundShiotani, B., & Zou, L. (2009) · Journal of Cell Science · doi:10.1242/jcs.035105 · Cited by 76 · see citing works
“Unlike RFC, which specifically recognizes 3 dsDNAssDNA junctions, the RAD17 complex preferentially recruits 9-1-1 complexes to 5 dsDNA-ssDNA junctions, which are associated with resected DSBs and stressed replication forks (Ellison and Stillman, 2003; Majka et al., 2006a; Zou et al., 2003).”
BackgroundReview: The lord of the rings: Structure and mechanism of the sliding clamp loader
Kelch, B. A. (2016) · Biopolymers · doi:10.1002/bip.22827 · Cited by 73 · see citing works
The fork and the kinase: A DNA replication tale from a CHK1 perspective
Besteiro, M. A. G., & Gottifredi, V. (2014) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2014.10.003 · Cited by 71 · see citing works
ATR kinase activation in G1 phase facilitates the repair of ionizing radiation-induced DNA damage
Gamper, A. M., Rofougaran, R., Watkins, S. C., Greenberger, J. S., Beumer, J. H., & Bakkenist, C. J. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt833 · Cited by 69 · see citing works
“The exact origin and structure of the RPA foci/ ssDNA we observed in G1 phase are presently unknown, but considering that the structure is not a result of HDR (or replication stall), the DNA might not have the 50-recessed junction, which is needed for loading of the 9-1-1 complex (31,32).”
Giannattasio, M., & Branzei, D. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2474-4 · Cited by 67 · see citing works
“Dpb11Cut5/TopBP1 (DNA Polymerase B subunit 11/Cell Untimely Turn 5/Topoisomerase II Binding Protein 1) [161, 162], Ddc1Rad9/RAD9 [163], Dna2 [164] and ETAA1 (Ewing Tumor Associated Antigen 1) [165, 166] have emerged as direct activators of the apical kinases Mec1, Rad3, and ATR through physical interactions (Fig.”
BackgroundInfluentialStructural Basis of Mec1-Ddc2-RPA Assembly and Activation on Single-Stranded DNA at Sites of Damage
Deshpande, I., Seeber, A., Shimada, K., Keusch, J. J., Gut, H., & Gasser, S. M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.019 · Cited by 63 · see citing works
“Similarly, the long unstructured C-terminal tail of 9-1-1 subunit Ddc1 can activate Mec1 kinase in vitro (Majka et al., 2006a), as well as in vivo, when artificially targeted together with Ddc2 to an integrated array of binding sites (Bonilla et al., 2008).”
BackgroundRPA Mediates Recruitment of MRX to Forks and Double-Strand Breaks to Hold Sister Chromatids Together
Seeber, A., Hegnauer, A. M., Hustedt, N., Deshpande, I., Poli, J., Eglinger, J., Pasero, P., Gut, H., Shinohara, M., Hopfner, K., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.10.032 · Cited by 66 · see citing works
“…for checkpoint and repair proteins, including but not limited toMec1-Ddc2 and 9-1-1, the DNA damage clamp, both at stalled forks and at DNA double-strand breaks (DSBs) (Paciotti et al., 2000; Rouse and Jackson, 2002; Xu et al., 2008; Zou and Elledge, 2003; Kanoh et al., 2006; Majka et al., 2006).”
BackgroundLoading clamps for DNA replication and repair
Bloom, L. B. (2009) · DNA repair · doi:10.1016/j.dnarep.2008.12.014 · Cited by 67 · see citing works
Dubrana, K., van Attikum, H., Hediger, F., & Gasser, S. M. (2007) · Journal of Cell Science · doi:10.1242/jcs.018366 · Cited by 64 · see citing works
“Indeed, activation of Mec1 in vitro depends on the appropriate loading of the Rad17-Mec3Ddc1 complex by Rad24 onto DNA (Majka et al., 2006b).”
BackgroundMethodInfluentialMammalian polymerase ζ is essential for post-replication repair of UV-induced DNA lesions
Jansen, J. G., Tsaalbi‐Shtylik, A., Hendriks, G., Verspuy, J. W. A., Gali, H., Haracska, L., & de Wind, N. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.09.006 · Cited by 63 · see citing works
Li, J., Holzschu, D. L., & Sugiyama, T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222241110 · Cited by 62 · see citing works
“Previous studies using the simple primed ssDNA substrates showed that the 3′-oriented loading of PCNA depends on RPA, which directionally binds to the ssDNA template (29, 38).”
BackgroundPCNA Loaders and Unloaders—One Ring That Rules Them All
Arbel, M., Choudhary, K., Tfilin, O., & Kupiec, M. (2021) · Genes · doi:10.3390/genes12111812 · Cited by 61 · see citing works
“Just artificially recruiting Ddc1 (one of the sunburnt in the 9-1-1) together with Ddc2 (the Mec1 partner) is enough to elicit the DRR [54] in the absence of DNA damage.”
BackgroundInfluentialReplication Checkpoint: Tuning and Coordination of Replication Forks in S Phase
Hustedt, N., Gasser, S. M., & Shimada, K. (2013) · Genes · doi:10.3390/genes4030388 · Cited by 57 · see citing works
“These structures, together with RPA, are sufficient to activate the ATR checkpoint in a cell-free system [37,50].”
BackgroundGenetic instability in budding and fission yeast—sources and mechanisms
Skoneczna, A., Kaniak, A., & Skoneczny, M. (2015) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuv028 · Cited by 57 · see citing works
“Then the authors compared the frequency of mutational changes within those sequences with their transcription levels and were able to demonstrate simultaneously for numerous loci that positive correlation between transcription and mutagenesis does exist.”
BackgroundInfluentialQuantitative sensing and signalling of single-stranded DNA during the DNA damage response
Bantele, S. C. S., Lisby, M., & Pfander, B. (2019) · Nature Communications · doi:10.1038/s41467-019-08889-5 · Cited by 51 · see citing works
Send in the Clamps: Control of DNA Translesion Synthesis in Eukaryotes
Jansen, J. G., Fousteri, M. I., & de Wind, N. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.005 · Cited by 54 · see citing works
Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends
Hirano, Y., & Sugimoto, K. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-12-1074 · Cited by 51 · see citing works
“The PCNA-like checkpoint clamps have been shown to target partial duplex DNA (Majka and Burgers, 2003; Majka et al., 2006).”
BackgroundStudying the DNA damage response using in vitro model systems
Garner, E., & Costanzo, V. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.04.015 · Cited by 47 · see citing works
Puddu, F., Piergiovanni, G., Plevani, P., & Muzi-Falconi, M. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002022 · Cited by 48 · see citing works
Limbo, O., Porter-Goff, M. E., Rhind, N., & Russell, P. R. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00994-10 · Cited by 48 · see citing works
“junctions (26, 48, 57), the ATR activating protein TopBP1”
BackgroundDiscovery of a Potent Stapled Helix Peptide That Binds to the 70N Domain of Replication Protein A
Frank, A. O., Vangamudi, B., Feldkamp, M. D., de Souza-Fagundes, E. M., Luzwick, J. W., Cortez, D., Olejniczak, E. T., Waterson, A. G., Rossanese, O. W., Chazin, W., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401730y · Cited by 47 · see citing works
RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling
Lindsey‐Boltz, L. A., Kemp, M. G., Capp, C., & Sancar, A. (2015) · Cell Cycle · doi:10.4161/15384101.2014.967076 · Cited by 46 · see citing works
Sugiyama, T., & Kantake, N. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.05.009 · Cited by 47 · see citing works
Burgoyne, P. S., Mahadevaiah, S. K., & Turner, J. M. A. (2007) · BioEssays · doi:10.1002/bies.20639 · Cited by 43 · see citing works
DDK Phosphorylates Checkpoint Clamp Component Rad9 and Promotes Its Release from Damaged Chromatin
Furuya, K., Miyabe, I., Tsutsui, Y., Paderi, F., Kakusho, N., Masai, H., Niki, H., & Carr, A. M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.026 · Cited by 42 · see citing works
“One potential function for DDK phosphorylation is thus to allow the DNA repair machinery to fully access the damage site by displacing 9-1-1 that sits at 50-DNA junction (Majka et al., 2006).”
BackgroundMultistep loading of a DNA sliding clamp onto DNA by replication factor C
Schrecker, M., Castaneda, J. C., Devbhandari, S., Kumar, C., Remus, D., & Hite, R. K. (2022) · eLife · doi:10.7554/elife.78253 · Cited by 42 · see citing works
“, 2003), Rad24- RFC loads the 9- 11 clamp at 5’ ss/dsDNA junctions (Ellison and Stillman, 2003; Castaneda et al., 2022; Majka et al., 2006), and Elg1- RFC appears to unload PCNA from dsDNA (Kubota et al.”
BackgroundWong, R. P. C., Petriukov, K. S., & Ulrich, H. D. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103163 · Cited by 40 · see citing works
Domenico, E. G. D., Romano, E., Porto, P. D., & Ascenzioni, F. (2014) · BioMed Research International · doi:10.1155/2014/787404 · Cited by 38 · see citing works
Assembly of Slx4 signaling complexes behind DNA replication forks
Balint, A., Kim, T. P., Gallo, D., Cussiol, J. R. R., de Oliveira, F. M. B., Yimit, A., Ou, J., Nakato, R., Gurevich, A., Shirahige, K., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201591190 · Cited by 39 · see citing works
“Phosphorylation of H2A by Mec1 is promoted by Ddc1, Dpb11, and Ddc2 (Majka et al , 2006b; Mordes et al , 2008; Navadgi-Patil & Burgers, 2008, 2009b; Puddu et al , 2011; Bandhu et al , 2014), but recruitment of Mec1 to lesions independent of Ddc1 and Dpb11 is sufficient for basal kinase activity and…”
InfluentialPeritore, M., Reußwig, K.-U., Bantele, S. C. S., Straub, T., & Pfander, B. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.02.005 · Cited by 39 · see citing works
Zheng, F., Georgescu, R. E., Yao, N. Y., Li, H., & O’Donnell, M. E. (2022) · eLife · doi:10.7554/elife.77469 · Cited by 38 · see citing works
“…3 ′ ss/ds DNA junctions to load the PCNA clamp for DNA polymerases and other proteins (Kelch et al., 2012b); while Rad24-RFC primarily targets a 5 ′ ss/ds DNA junction for loading the 9-1-1 clamp to stimulate the ATR kinase (Ellison and Stillman, 2003; Majka et al., 2006; Majka and Burgers, 2003).”
BackgroundInfluentialHARPing on about the DNA damage response during replication: Figure 1.Preprint
Driscoll, R., & Cimprich, K. A. (2009) · Genes & Development · doi:10.1101/gad.1860609 · Cited by 38 · see citing works
“In the presence of RPA, this is thought to occur on the 59-primer end (Ellison and Stillman 2003; Majka et al. 2006).”
BackgroundSeparable roles for Mec1/ATR in genome maintenance, DNA replication, and checkpoint signalingPreprint
Lanz, M. C., Oberly, S., Sanford, E. J., Sharma, S., Chabes, A., & Smolka, M. B. (2018) · Genes & Development · doi:10.1101/gad.308148.117 · Cited by 37 · see citing works
“Ddc1 is a component of the yeast 9-1-1 DNA clamp that is loaded at the 5′ end of dsDNA:ssDNA junctions (Majka et al. 2006).”
BackgroundResultInfluentialKelly, R. M., & Davey, S. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0085859 · Cited by 36 · see citing works
Mechanisms of loading and release of the 9-1-1 checkpoint clamp
Castaneda, J. C., Schrecker, M., Remus, D., & Hite, R. K. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00741-7 · Cited by 37 · see citing works
“ATRMec1 activation occurs specifically on replication protein A (RPA)-coated single-stranded DNA (ssDNA) adjacent to 5’ single-stranded/double-stranded DNA (ss/dsDNA) junctions that serve as a loading site for the 9-1-1 checkpoint clamp, which mediates ATRMec1 activation (4-6).”
BackgroundUbiquitin and SUMO signalling in DNA repair
Thomson, T. M., & Guerra‐Rebollo, M. (2010) · Biochemical Society Transactions · doi:10.1042/bst0380116 · Cited by 34 · see citing works
Day, M., Oliver, A. W., & Pearl, L. H. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac588 · Cited by 34 · see citing works
“…at sites of ssDNA is dependent on the RAD9–RAD1–HUS1 (9–1–1) heterotrimeric checkpoint clamp (11) preferentially loaded at a 5 -recessed margin (12,13) by a specialised form of the het-eropentameric AAA+ Replication Factor C (RFC) clamp loader in which the large RFC1 subunit, required for loading…”
Rescue of replication failure by Fanconi anaemia proteins
Constantinou, A. (2011) · Chromosoma · doi:10.1007/s00412-011-0349-2 · Cited by 34 · see citing works
“The 5′ junction between ssDNA and dsDNA is recognised by RAD17RFC, which loads the 9–1–1 checkpoint clamp necessary for efficient ATR activation (Ellison and Stillman 2003; Majka et al. 2006; Zou et al. 2003).”
BackgroundFunctions of Multiple Clamp and Clamp-Loader Complexes in Eukaryotic DNA Replication
Ohashi, E., & Tsurimoto, T. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-6955-0_7 · Cited by 32 · see citing works
Cell-cycle-specific activators of the Mec1/ATR checkpoint kinase
Navadgi, V. M., & Burgers, P. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390600 · Cited by 34 · see citing works
Self-citationDNA Damage and Replication Stress Checkpoints
Yates, L. A., Zhang, X., & Burgers, P. (2025) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-072324-031915 · Cited by 37 · see citing works
Self-citationDhingra, N., Wei, L., & Zhao, X. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006006 · Cited by 33 · see citing works
“9-1-1 then promotes Mec1 activation via allosteric stimulation of its kinase activity (6, 7).”
BackgroundFumarase is involved in DNA double-strand break resection through a functional interaction with Sae2
Leshets, M., Ramamurthy, D., Lisby, M., Lehming, N., & Pines, O. (2017) · Current Genetics · doi:10.1007/s00294-017-0786-4 · Cited by 32 · see citing works
The helicase Pif1 functions in the template switching pathway of DNA damage bypass
García‐Rodríguez, N., Wong, R. P. C., & Ulrich, H. D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky648 · Cited by 31 · see citing works
“Notably, this model is analogous to a scenario that might apply at the 5′-junction of the gap, the loading site of the 9–1-1 checkpoint clamp (43,44).”
MethodDNA is loaded through the 9-1-1 DNA checkpoint clamp in the opposite direction of the PCNA clamp
Zheng, F., Georgescu, R. E., Yao, N. Y., O’Donnell, M. E., & Li, H. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00742-6 · Cited by 32 · see citing works
Ddc2 Mediates Mec1 Activation through a Ddc1- or Dpb11-Independent Mechanism
Bandhu, A., Kang, J., Fukunaga, K., Goto, G. H., & Sugimoto, K. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004136 · Cited by 31 · see citing works
Alver, R. C., Zhang, T., Josephrajan, A., Fultz, B. L., Hendrix, C. J., Das‐Bradoo, S., & Bielinsky, A. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku479 · Cited by 31 · see citing works
Depletion of RAD17 sensitizes pancreatic cancer cells to gemcitabine
Fredebohm, J., Wolf, J. M., Hoheisel, J. D., & Boettcher, M. (2013) · Journal of Cell Science · doi:10.1242/jcs.124768 · Cited by 30 · see citing works
Lindsey‐Boltz, L. A., Reardon, J. T., Wold, M. S., & Sancar, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407825 · Cited by 30 · see citing works
“Phosphorylation of RPA modulates RPA interactions with checkpoint and other proteins (8, 10, 55).”
BackgroundSelf-citationHuman Exonuclease 5 Is a Novel Sliding Exonuclease Required for Genome Stability
Sparks, J. L., Kumar, R., Singh, M. K., Wold, M. S., Pandita, T. K., & Burgers, P. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.422444 · Cited by 30 · see citing works
“Directionality enforcement by RPA has been demonstrated previously for enzymes and factors involved in nucleotide excision repair and in theDNAdamage checkpoint, re-emphasizing the importance in carrying out these type of in vitro studies with the cognate form of RPA (29, 30).”
BackgroundSelf-citationArranging eukaryotic nuclear DNA polymerases for replication
Kunkel, T. A., & Burgers, P. (2017) · BioEssays · doi:10.1002/bies.201700070 · Cited by 30 · see citing works
“Examples are the checkpoint clamp 9-1-1 and Dna2 nuclease, which show promiscuous directionality on naked ssDNA but unique directionality on RPA-coated DNA [30, 31].”
BackgroundSelf-citationMolecular Mechanisms of DNA Replication Checkpoint Activation
Recolin, B., van der Laan, S., Tsanov, N., & Maiorano, D. (2014) · Genes · doi:10.3390/genes5010147 · Cited by 29 · see citing works
“cerevisiae, see Table 1) [113].”
9-1-1: PCNA's specialized cousin
Eichinger, C. S., & Jentsch, S. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.08.002 · Cited by 29 · see citing works
Theis, J. F., Irene, C., Dershowitz, A., Brost, R. L., Tobin, M. L., di Sanzo, F. M., Wang, J.-Y., Boone, C. M., & Newlon, C. S. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001227 · Cited by 29 · see citing works
“. Binding of the Rad17p-Ddc1p-Mec3p clamp results in activation of Mec1p kinase activity. Ddc1p is phosphorylated by Mec1p”
BackgroundThe Rad4TopBP1 ATR-Activation Domain Functions in G1/S Phase in a Chromatin-Dependent Manner
Lin, S.-J., Wardlaw, C. P., Morishita, T., Miyabe, I., Chahwan, C., Caspari, T., Schmidt, U. G., Carr, A. M., & Garcia, V. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002801 · Cited by 28 · see citing works
Recolin, B., van der Laan, S., & Maiorano, D. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1241 · Cited by 28 · see citing works
“We propose that the essential role of RPA in checkpoint signaling is to stabilize DNA polymerase-a at stalled forks and promote synthesis of single-stranded/double-stranded DNA hybrids as well as recruitment of the 9-1-1 complex onto this substrate mediated by Rad17, as previously suggested (8,12,16,17).”
MethodYet another job for Dna2: checkpoint activation
Wanrooij, P. H., & Burgers, P. (2015) · DNA Repair · doi:10.1016/j.dnarep.2015.04.009 · Cited by 35 · see citing works
“Conversely, Dna2 prefers 5′-flap structures [18,72].”
Self-citationSong, W., Pascal, J. M., Ellenberger, T., & Tomkinson, A. E. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.05.002 · Cited by 27 · see citing works
- Authors
- Majka, J., Binz, S. K., Wold, M. S., & Burgers, P. M. J.
- Affiliations
- Washington University in St. Louis (US)
- University of Iowa (US)
- Corresponding author
- Burgers, Peter M.J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 281
- Issue
- 38
- Pages
- 27855-27861
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2161481116
- Cited by
- 205
- References
- 43
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 10 · 2023: 3 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 8 · 2015: 12 · 2014: 16 · 2013: 13 · 2012: 9
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM44721, GM-32431, R01GM044721, R01GM032431)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- replication protein A, clamp loading, DNA damage response, single-stranded DNA binding protein, Saccharomyces cerevisiae
- MeSH terms
- Adenosine Triphosphatases, DNA Damage, DNA Helicases, DNA-Binding Proteins, Endonucleases, Nuclear Proteins, Substrate Specificity, Cell Cycle Proteins, Proliferating Cell Nuclear Antigen, Saccharomyces cerevisiae Proteins, DNA Repair Enzymes, Intracellular Signaling Peptides and Proteins, Replication Protein A, Replication Protein C
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
