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Requirement of the Mre11 Complex and Exonuclease 1 for Activation of the Mec1 Signaling Pathway
Open accessAbstract
The large protein kinases, ataxia-telangiectasia mutated (ATM) and ATM-Rad3-related (ATR), orchestrate DNA damage checkpoint pathways. In budding yeast, ATM and ATR homologs are encoded by TEL1 and MEC1, respectively. The Mre11 complex consists of two highly related proteins, Mre11 and Rad50, and a third protein, Xrs2 in budding yeast or Nbs1 in mammals. The Mre11 complex controls the ATM/Tel1 signaling pathway in response to double-strand break (DSB) induction. We show here that the Mre11 complex functions together with exonuclease 1 (Exo1) in activation of the Mec1 signaling pathway after DNA damage and replication block. Mec1 controls the checkpoint responses following UV irradiation as well as DSB induction. Correspondingly, the Mre11 complex and Exo1 play an overlapping role in activation of DSB- and UV-induced checkpoints. The Mre11 complex and Exo1 collaborate in producing long single-stranded DNA (ssDNA) tails at DSB ends and promote Mec1 association with the DSBs. The Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway. However, Ddc1 association with DSBs does not require the function of the Mre11 complex and Exo1. Mec1 controls checkpoint responses to stalled DNA replication as well. Accordingly, the Mre11 complex and Exo1 contribute to activation of the replication checkpoint pathway. Our results provide a model in which the Mre11 complex and Exo1 cooperate in generating long ssDNA tracts and thereby facilitate Mec1 association with sites of DNA damage or replication block.
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In the citing paper
“This work shows that UV irradiation causes the accumulation, in yeast chromosomes, of long ssDNA regions that are dependent upon NER and Exo1 and correlate with Mec1 kinase activation.”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [60]
In the citing paper
“In order to achieve a full and prompt checkpoint activity after UV irradiation in non cycling yeast cells, NER is necessary but not sufficient: in fact, the nuclease activity of Exo1 is also required [60,61].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [60]
In the citing paper
“Recent work shed light on these problems, showing that normal NER-intermediates are not directly responsible for activating checkpoint kinases.”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [60]
In the citing paper
“DNA nucleases (such as DNA2 and Exo1) also contribute to the DSB end resection and subsequent ATM-ATR transition [221]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [221]
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Citations
Cites
Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. (2005) · doi:10.1128/9781555816704 · Cited by 5,683
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466
The DNA damage response: putting checkpoints in perspective
Zhou, B.-B. S., & Elledge, S. J. (2000) · Nature · doi:10.1038/35044005 · Cited by 3,213
Gietz, R. D., & Sugino, A. (1988) · Gene · doi:10.1016/0378-1119(88)90185-0 · Cited by 2,851
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
Bootsma, D., & Hoeijmakers, J. H. J. (1996) · Trends in Genetics · doi:10.1016/0168-9525(96)81408-9 · Cited by 2,285
Cell Cycle Checkpoints: Preventing an Identity Crisis
Elledge, S. J. (1996) · Science · doi:10.1126/science.274.5293.1664 · Cited by 2,050
Cell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966
Wold, M. S. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.61 · Cited by 1,445
Molecular mechanism of nucleotide excision repair
de Laat, W. L., Jaspers, N. G. J., & Hoeijmakers, J. H. J. (1999) · Genes & Development · doi:10.1101/gad.13.7.768 · Cited by 1,122
Requirement of the MRN complex for ATM activation by DNA damage
Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., & Shiloh, Y. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg541 · Cited by 1,075
ATR and ATRIP: Partners in Checkpoint Signaling
Cortez, D., Guntuku, S., Qin, J., & Elledge, S. J. (2001) · Science · doi:10.1126/science.1065521 · Cited by 985
The MRE11 complex: at the crossroads of DNA repair and checkpoint signalling
D'Amours, D., & Jackson, S. P. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm805 · Cited by 874
Lee, S. E., Moore, J. K., Holmes, A. M., Umezu, K., Kolodner, R. D., & Haber, J. E. (1998) · Cell · doi:10.1016/s0092-8674(00)81482-8 · Cited by 784
The many substrates and functions of ATM.
Kastan, M. B., & Lim, D.-S. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043058 · Cited by 779
Direct Activation of the ATM Protein Kinase by the Mre11/Rad50/Nbs1 Complex
Lee, J.-H., & Paull, T. T. (2004) · Science · doi:10.1126/science.1091496 · Cited by 762
Zhao, X., Muller, E. G. D., & Rothstein, R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80277-4 · Cited by 728
S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex
Katou, Y., Kanoh, Y., Bando, M., Noguchi, H., Tanaka, H., Ashikari, T., Sugimoto, K., & Shirahige, K. (2003) · Nature · doi:10.1038/nature01900 · Cited by 649
Self-citationRegulation of RAD53 by the ATM -Like Kinases MEC1 and TEL1 in Yeast Cell Cycle Checkpoint Pathways
Sanchez, Y., Desany, B. A., Jones, W. J., Liu, Q., Wang, B., & Elledge, S. J. (1996) · Science · doi:10.1126/science.271.5247.357 · Cited by 585
Control of the DNA damage checkpoint by Chk1 and Rad53 protein kinases through distinct mechanisms
Sanchez, Y., Bachant, J., Wang, H., Hu, F., Liu, D., Tetzlaff, M., & Elledge, S. J. (1999) · Science · doi:10.1126/science.286.5442.1166 · Cited by 536
Phosphorylation of SMC1 is a critical downstream event in the ATM–NBS1–BRCA1 pathwayPreprint
Kitagawa, R., Bakkenist, C. J., McKinnon, P. J., & Kastan, M. B. (2004) · Genes & Development · doi:10.1101/gad.1200304 · Cited by 535
The Mre11 complex is required for ATM activation and the G2/M checkpoint
Carson, C. T., Schwartz, R. A., Stracker, T. H., Lilley, C. E., Lee, D. V., & Weitzman, M. D. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg630 · Cited by 502
Moreau, S., Ferguson, J. R., & Symington, L. S. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.556 · Cited by 447
CDC5 and CKII Control Adaptation to the Yeast DNA Damage Checkpoint
Toczyski, D. P., Galgoczy, D. J., & Hartwell, L. H. (1997) · Cell · doi:10.1016/s0092-8674(00)80375-x · Cited by 431
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
Haber, J. E. (1998) · Cell · doi:10.1016/s0092-8674(00)81626-8 · Cited by 406
Intermediates of recombination during mating type switching in Saccharomyces cerevisiae.
White, C. I., & Haber, J. E. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb08158.x · Cited by 391
A DNA Damage Response Pathway Controlled by Tel1 and the Mre11 Complex
Usui, T., Ogawa, H., & Petrini, J. H. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00270-2 · Cited by 384
Two checkpoint complexes are independently recruited to sites of DNA damage in vivo
Melo, J. A., Cohen, J., & Toczyski, D. P. (2001) · Genes & Development · doi:10.1101/gad.903501 · Cited by 384
Greenwell, P. W., Kronmal, S., Porter, S. E., Gassenhuber, J., Obermaier, B., & Petes, T. D. (1995) · Cell · doi:10.1016/0092-8674(95)90479-4 · Cited by 382
Osborn, A. J., & Elledge, S. J. (2003) · Genes & Development · doi:10.1101/gad.1098303 · Cited by 378
Morrow, D. M., Tagle, D. A., Shiloh, Y., Collins, F. S., & Hieter, P. (1995) · Cell · doi:10.1016/0092-8674(95)90480-8 · Cited by 370
Ellison, V., & Stillman, B. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000033 · Cited by 363
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
ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanismPreprint
Nakada, D., Matsumoto, K., & Sugimoto, K. (2003) · Genes & Development · doi:10.1101/gad.1099003 · Cited by 306
Self-citationPellicioli, 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
Vialard, J., Gilbert, C. S., Green, C. M., & Lowndes, N. F. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5679 · Cited by 284
Ritchie, K. B., Mallory, J. C., & Petes, T. D. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.6065 · Cited by 265
Recruitment of Mec1 and Ddc1 Checkpoint Proteins to Double-Strand Breaks Through Distinct Mechanisms
Kondo, T., Wakayama, T., Naiki, T., Matsumoto, K., & Sugimoto, K. (2001) · Science · doi:10.1126/science.1063827 · Cited by 258
Self-citationYeast 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
Paciotti, V., Clerici, M., Lucchini, G., & Longhese, M. P. (2000) · Genes & Development · doi:10.1101/gad.14.16.2046 · Cited by 246
Ivanov, E. L., Sugawara, N., White, C. I., Fabre, F., & Haber, J. E. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.5.3414-3425.1994 · Cited by 243
Mre11 Protein Complex Prevents Double-Strand Break Accumulation during Chromosomal DNA Replication
Costanzo, V., Robertson, K., Bibikova, M., Kim, E., Grieco, D., Gottesman, M., Carroll, D., & Gautier, J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00294-5 · Cited by 239
The Mre11 complex and ATM: collaborating to navigate S phase
Petrini, J. H. J. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00091-0 · Cited by 233
The yeast Xrs2 complex functions in S phase checkpoint regulation
D'Amours, D., & Jackson, S. P. (2001) · Genes & Development · doi:10.1101/gad.208701 · Cited by 228
Tsubouchi, H., & Ogawa, H. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.7.2221 · Cited by 217
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
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
Exonuclease I of Saccharomyces cerevisiae Functions in Mitotic Recombination In Vivo and In Vitro
Fiorentini, P., Huang, K. N., Tishkoff, D. X., Kolodner, R. D., & Symington, L. S. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.5.2764 · Cited by 198
Checkpoint activation in response to double-strand breaks requires the Mre11/Rad50/Xrs2 complex
Grenon, M., Gilbert, C., & Lowndes, N. F. (2001) · Nature Cell Biology · doi:10.1038/ncb0901-844 · Cited by 184
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
Moreau, S., Morgan, E. A., & Symington, L. S. (2001) · Genetics · doi:10.1093/genetics/159.4.1423 · Cited by 176
Lucca, C., Vanoli, F., Cotta‐Ramusino, C., Pellicioli, A., Liberi, G., Haber, J. E., & Foiani, M. (2003) · Oncogene · doi:10.1038/sj.onc.1207199 · Cited by 173
Ritchie, K. B., & Petes, T. D. (2000) · Genetics · doi:10.1093/genetics/155.1.475 · Cited by 173
DNA damage checkpoint in budding yeast
Longhese, M. P., Foiani, M., Muzi-Falconi, M., Lucchini, G., & Plevani, P. (1998) · The EMBO Journal · doi:10.1093/emboj/17.19.5525 · Cited by 162
Tishkoff, D. X., Amin, N. S., Viars, C. S., Arden, K. C., & Kolodner, R. D. (1998) · PubMed · Cited by 158
Rouse, J. W., & Jackson, S. P. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5801 · Cited by 139
Altering telomere structure allows telomerase to act in yeast lacking ATM kinases
Chan, S. W. L., Chang, J. Y., Prescott, J. C., & Blackburn, E. H. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00391-8 · Cited by 119
Wakayama, T., Kondo, T., Ando, S., Matsumoto, K., & Sugimoto, K. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.755-764.2001 · Cited by 117
Self-citationNon‐enzymatic triggering of the ceramide signalling cascade by solar UVA radiation
Grether‐Beck, S., Bonizzi, G., Schmitt‐Brenden, H., Felsner, I., Timmer, A., Sies, H., Johnson, J. P., Piette, J. G., & Krutmann, J. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5793 · Cited by 114
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
Takata, H., Kanoh, Y., Gunge, N., Shirahige, K., & Matsuura, A. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00262-x · Cited by 95
Naiki, T., Shimomura, T., Kondo, T., Matsumoto, K., & Sugimoto, K. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.16.5888-5896.2000 · Cited by 84
Self-citationLee, S. E., Bressan, D. A., Petrini, J. H. J., & Haber, J. E. (2002) · DNA repair · doi:10.1016/s1568-7864(01)00003-9 · Cited by 73
Nakada, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg252 · Cited by 62
Self-citationAssociation of Rad9 with Double-Strand Breaks through a Mec1-Dependent Mechanism
Naiki, T., Wakayama, T., Nakada, D., Matsumoto, K., & Sugimoto, K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3277-3285.2004 · Cited by 54
Self-citationQiu, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.13.3077 · Cited by 42
Zhang, H., Taylor, J., & Siede, W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300061200 · Cited by 24
Research works printed but not linked: 1
- Tishkoff, D. X., Amin N. S., Viars C. S., Arden K. C., and Kolodner R. D.. 1998. Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease. Cancer Res. 58:5027–5031.
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Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G. C. M., Lukas, J., & Jackson, S. P. (2006) · Nature Cell Biology · doi:10.1038/ncb1337 · Cited by 1,064
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Gravel, S., Chapman, J. R., Magill, C. P., & Jackson, S. P. (2008) · Genes & Development · doi:10.1101/gad.503108 · Cited by 595
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Metadata
- Authors
- Nakada, D., Hirano, Y., & Sugimoto, K.
- Affiliations
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Sugimoto, Katsunori
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-11
- Volume
- 24
- Issue
- 22
- Pages
- 10016-10025
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC525484
- OpenAlex
- W2110555186
- Cited by
- 113
- References
- 68
- Citations by year
- 2023: 2 · 2022: 1 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 9 · 2012: 4
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- 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
- Mre11 complex, EXO1, Mec1, DNA damage checkpoint, DNA double-strand breaks, single-stranded DNA, DNA end resection, S-phase checkpoint, UV-induced DNA damage, Tel1, Saccharomyces cerevisiae
- MeSH terms
- DNA Damage, DNA Replication, DNA-Binding Proteins, DNA, Fungal, Endodeoxyribonucleases, Exodeoxyribonucleases, Fungal Proteins, Genes, Fungal, Models, Biological, Mutation, Phleomycins, Phosphoproteins, Phosphorylation, Saccharomyces cerevisiae, Transcription Factors, Signal Transduction, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Replication Protein A, Checkpoint Kinase 2
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