A Suppressor of Two Essential Checkpoint Genes Identifies a Novel Protein that Negatively Affects dNTP Pools
Open accessAbstract
In Saccharomyces cerevisiae, MEC1 and RAD53 are essential for cell growth and checkpoint function. Their essential role in growth can be bypassed by deletion of a novel gene, SML1, which functions after several genes whose overexpression also suppresses mec1 inviability. In addition, sml1 affects various cellular processes analogous to overproducing the large subunit of ribonucleotide reductase, RNR1. These include effects on mitochondrial biogenesis, on the DNA damage response, and on cell growth. Consistent with these observations, the levels of dNTP pools in sml1 delta strains are increased compared to wild-type. This effect is not due to an increase in RNR transcription. Finally, both in vivo and in vitro experiments show that Sml1 binds to Rnr1. We propose that Sml1 inhibits dNTP synthesis posttranslationally by binding directly to Rnr1 and that Mec1 and Rad53 are required to relieve this inhibition.
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Deletion of SML1 is necessary to suppress the lethality of MEC1 deletion.
“a mec1Δ sml1Δ double mutant strain (deletion of SML1 is necessary to suppress the lethality of MEC1 deletion [66])”
From A Role for Checkpoint Kinase-Dependent Rad26 Phosphorylation in Transcription-Coupled DNA Repair in <i>Saccharomyces cerevisiae</i> (2010) · cites this paper as [66]
Cites
Antibodies, a laboratory manual
(1989) · Biomedicine & Pharmacotherapy · doi:10.1016/0753-3322(89)90130-3 · Cited by 12,318 · see citing works
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 · see citing works
Antibodies: A laboratory manual
J.L. (1989) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(89)90307-1 · Cited by 5,141 · see citing works
[12] One-step gene disruption in yeast
Rothstein, R. J. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)01015-0 · Cited by 3,282 · see citing works
Self-citationGenomic Libraries and a Host Strain Designed for Highly Efficient Two-Hybrid Selection in Yeast
James, P. M., Halladay, J. T., & Craig, E. A. (1996) · Genetics · doi:10.1093/genetics/144.4.1425 · Cited by 2,638 · see citing works
Boeke, J. D., Lacroute, F., & Fink, G. R. (1984) · Molecular and General Genetics MGG · doi:10.1007/bf00330984 · Cited by 2,354 · see citing works
Bootsma, D., & Hoeijmakers, J. H. J. (1996) · Trends in Genetics · doi:10.1016/0168-9525(96)81408-9 · Cited by 2,285 · see citing works
Cell Cycle Checkpoints: Preventing an Identity Crisis
Elledge, S. J. (1996) · Science · doi:10.1126/science.274.5293.1664 · Cited by 2,047 · see citing works
Elevated recombination rates in transcriptionally active DNA
Thomas, B. J., & Rothstein, R. J. (1989) · Cell · doi:10.1016/0092-8674(89)90584-9 · Cited by 1,633 · see citing works
Self-citationHigh-frequency transformation of yeast: autonomous replication of hybrid DNA molecules.
Struhl, K., Stinchcomb, D. T., Scherer, S., & Davis, R. W. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.3.1035 · Cited by 1,456 · see citing works
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,450 · see citing works
A simple and efficient method for direct gene deletion inSaccharomyces cerevisiae
Baudin‐Baillieu, A., Ozier-Kalogéropoulos, O., DENOUEL, A., Lacroute, F., & Cullin, C. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.14.3329 · Cited by 1,268 · see citing works
Xu, Y., Ashley, T., Brainerd, E. E., Bronson, R. T., Meyn, M. S., & Baltimore, D. (1996) · Genes & Development · doi:10.1101/gad.10.19.2411 · Cited by 830 · see citing works
INTERACTIONS BETWEEN DEOXYRIBONUCLEOTIDE AND DNA SYNTHESIS
Reichard, P. A. (1988) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.57.070188.002025 · Cited by 773 · see citing works
Weinert, T. A., Kiser, G. L., & Hartwell, L. H. (1994) · Genes & Development · doi:10.1101/gad.8.6.652 · Cited by 750 · see citing works
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 · see citing works
Plasmid construction by homologous recombination in yeast
Ma, H., Kunes, S. M., Schatz, P. J., & Botstein, D. (1987) · Gene · doi:10.1016/0378-1119(87)90376-3 · Cited by 563 · see citing works
Pleiotropic defects in ataxia-telangiectasia protein-deficient mice
Elson, A., Wang, Y., Daugherty, C., Morton, C. C., Zhou, F., Campos-Torres, J., & Leder, P. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13084 · Cited by 498 · see citing works
Allen, J. B., Zhou, Z. Y., Siede, W., Friedberg, E. C., & Elledge, S. J. (1994) · Genes & Development · doi:10.1101/gad.8.20.2401 · Cited by 497 · see citing works
ATAXIA-TELANGIECTASIA AND THE NIJMEGEN BREAKAGE SYNDROME: Related Disorders But Genes Apart
Shiloh, Y. (1997) · Annual Review of Genetics · doi:10.1146/annurev.genet.31.1.635 · Cited by 482 · see citing works
[57] Genetic and physical maps of Saccharomyces cerevisiae
Mortimer, R., Schild, D., Contopoulou, C. R., & Kans, J. A. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)94060-p · Cited by 473 · see citing works
Dual roles of ATM in the cellular response to radiation and in cell growth control.Preprint
Xu, Y., & Baltimore, D. (1996) · Genes & Development · doi:10.1101/gad.10.19.2401 · Cited by 402 · see citing works
A Role for the Transcription Factors Mbp1 and Swi4 in Progression from G1 to S Phase
Koch, C., Moll, T., Neuberg, M., Ahorn, H., & Nasmyth, K. (1993) · Science · doi:10.1126/science.8372350 · Cited by 382 · see citing works
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 · see citing works
The Schizosaccharomyces pombe rad3 checkpoint gene.
Bentley, N. J., Holtzman, D. A., Flaggs, G., Keegan, K. S., DeMaggio, A. J., Ford, J. C., Hoekstra, M. F., & Carr, A. M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01054.x · Cited by 366 · see citing works
DUN1 encodes a protein kinase that controls the DNA damage response in yeast
Zhou, Z. Y., & Elledge, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)90321-g · Cited by 346 · see citing works
Use of polymerase chain reaction epitope tagging for protein tagging in Saccharomyces cerevisiae
Schneider, B. L., Seufert, W., Steiner, B., Yang, Q. H., & Futcher, A. B. (1995) · Yeast · doi:10.1002/yea.320111306 · Cited by 314 · see citing works
Ribonucleotide reductase: regulation, regulation, regulation
Elledge, S. J., Zhou, Z. Y., & Allen, J. B. (1992) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(92)90249-9 · Cited by 310 · see citing works
Genetic analysis of the mitotic transmission of minichromosomes
Koshland, D. E. (1985) · Cell · doi:10.1016/0092-8674(85)90153-9 · Cited by 304 · 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
Methods in yeast genetics : a Cold Spring Harbor Laboratory course manual
Adams, A. E. (1998) · Medical Entomology and Zoology · Cited by 293 · see citing works
Vectors for the inducible overexpression of glutathione S‐transferase fusion proteins in yeast
Mitchell, D. A., Marshall, T. K., & Deschenes, R. J. (1993) · Yeast · doi:10.1002/yea.320090705 · Cited by 286 · see citing works
Keegan, K. S., Holtzman, D. A., Plug, A. W., Christenson, E., Brainerd, E. E., Flaggs, G., Bentley, N. J., Taylor, E. M., Meyn, M. S., Moss, S. B., et al. (1996) · Genes & Development · doi:10.1101/gad.10.19.2423 · Cited by 283 · see citing works
Murray, A. W. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90059-0 · Cited by 281 · see citing works
ATM-related genes: What do they tell us about functions of the human gene?
Zakian, V. A. (1995) · Cell · doi:10.1016/0092-8674(95)90463-8 · Cited by 271 · see citing works
DNA damage and cell cycle regulation of ribonucleotide reductase
Elledge, S. J., Zhou, Z., Allen, J. B., & Navas, T. A. (1993) · BioEssays · doi:10.1002/bies.950150507 · Cited by 242 · see citing works
Studies of Gene Mutation in SaccharomycesPreprint
Roman, H. (1956) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1956.021.01.015 · Cited by 229 · see citing works
Genetic and physical maps of Saccharomyces cerevisiae
Cherry, J. M., Ball, C. A., Weng, S., Juvik, G., Schmidt, R., Adler, C., Dunn, B. L., Dwight, S. S., Riles, L., Mortimer, R., et al. (1997) · Nature · doi:10.1038/387s067 · Cited by 222 · see citing works
Kato, R., & Ogawa, H. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.15.3104 · Cited by 218 · see citing works
Elledge, S. J., & Davis, R. W. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.8.2783-2793.1987 · Cited by 204 · see citing works
Paulovich, A. G., Margulies, R. U., Garvik, B. M., & Hartwell, L. H. (1997) · Genetics · doi:10.1093/genetics/145.1.45 · Cited by 196 · see citing works
Huang, M., & Elledge, S. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.10.6105 · Cited by 177 · see citing works
Wang, Y., Elson, A., & Leder, P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14590 · Cited by 170 · see citing works
DNA Damage Induction of Ribonucleotide Reductase
Elledge, S. J., & Davis, R. W. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.11.4932-4940.1989 · Cited by 126 · see citing works
South African museums' status ‘at risk’
Cherry, M. L. (1997) · Nature · doi:10.1038/43025 · Cited by 122 · see citing works
Rnr4p, a Novel Ribonucleotide Reductase Small-Subunit Protein
Wang, P. J., Chabes, A., Casagrande, R. J., Tian, X. C., Thelander, L., & Huffaker, T. C. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.10.6114 · Cited by 120 · see citing works
Zheng, P., Fay, D. S., Burton, J. L., Xiao, H., Pinkham, J. L., & Stern, D. F. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.9.5829 · Cited by 104 · see citing works
Westphal, C. H., Schmaltz, C., Rowan, S., Elson, A., Fisher, D. E., & Leder, P. (1997) · PubMed · Cited by 81 · see citing works
Mutations in SPK1/RAD53 that specifically abolish checkpoint but not growth-related functions
Fay, D. S., Sun, Z., & Stern, D. F. (1997) · Current Genetics · doi:10.1007/s002940050181 · Cited by 56 · see citing works
Muller, E. G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)51107-3 · Cited by 42 · see citing works
Self-citationLecrenier, N., & Foury, F. (1995) · Molecular and General Genetics MGG · doi:10.1007/bf00290229 · Cited by 39 · see citing works
Cross, D. R., Miller, B., & James, S. J. (1993) · Cell Proliferation · doi:10.1111/j.1365-2184.1993.tb00328.x · Cited by 35 · see citing works
Nasr, F., Bécam, A. ‐., Słonimski, P. P., & Herbert, C. J. (1994) · PubMed · Cited by 16 · see citing works
Danilevskaya, O. N., Kurenova, E., Leibovitch, B. A., et al. (1984) · Molecular and General Genetics MGG · doi:10.1007/bf00330983 · Cited by 12 · see citing works
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Cimprich, K. A., & Cortez, D. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2450 · Cited by 1,798 · see citing works
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 · see citing works
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Usui, T., Ogawa, H., & Petrini, J. H. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00270-2 · Cited by 384 · see citing works
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Melo, J. A., Cohen, J., & Toczyski, D. P. (2001) · Genes & Development · doi:10.1101/gad.903501 · Cited by 384 · see citing works
Mills, K. D., Sinclair, D. A., & Guarente, L. (1999) · Cell · doi:10.1016/s0092-8674(00)80772-2 · Cited by 334 · see citing works
Buisson, R., Boisvert, J. L., Benes, C. H., & Zou, L. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.07.029 · Cited by 316 · see citing works
The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1
Zhao, X., & Rothstein, R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062502299 · Cited by 290 · see citing works
Self-citationDNA Damage Response: Three Levels of DNA Repair Regulation
Sirbu, B. M., & Cortez, D. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012724 · Cited by 272 · see citing works
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 · see citing works
Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation
Sweeney, F. D., Yang, F., Chi, A., Shabanowitz, J., Hunt, D. F., & Durocher, D. (2005) · Current Biology · doi:10.1016/j.cub.2005.06.063 · Cited by 237 · see citing works
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Cortez, D. (2015) · DNA Repair · doi:10.1016/j.dnarep.2015.04.026 · Cited by 223 · see citing works
A two-step model for senescence triggered by a single critically short telomere
Abdallah, P., Luciano, P., Runge, K. W., Lisby, M., Géli, V., Gilson, E., & Teixeira, M. T. (2009) · Nature Cell Biology · doi:10.1038/ncb1911 · Cited by 190 · see citing works
Epigenetic silencing mediates mitochondria stress-induced longevity
Schroeder, E. A., Raimundo, N., & Shadel, G. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.003 · Cited by 186 · see citing works
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Morin, I., Ngo, H., Greenall, A., Zubko, M. K., Morrice, N., & Lydall, D. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.171 · Cited by 164 · see citing works
Yao, R., Zhang, Z., An, X., Bucci, B., Perlstein, D. L., Stubbe, J., & Huang, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1131932100 · Cited by 151 · see citing works
Enomoto, S., Glowczewski, L., & Berman, J. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.02-02-0012 · Cited by 133 · see citing works
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Zegerman, P., & Diffley, J. F. X. (2009) · DNA Repair · doi:10.1016/j.dnarep.2009.04.023 · Cited by 128 · see citing works
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Serero, A., Jubin, C., Loeillet, S., Legoix-Né, P., & Nicolas, A. G. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314423111 · Cited by 126 · see citing works
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McAinsh, A. D., Scott-Drew, S., Murray, J. A. H., & Jackson, S. P. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80424-2 · Cited by 115 · see citing works
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Nakada, D., Hirano, Y., & Sugimoto, K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.22.10016-10025.2004 · Cited by 113 · see citing works
Perspectives on the DNA damage and replication checkpoint responses in Saccharomyces cerevisiae
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Sabbioneda, S., Bortolomai, I., Giannattasio, M., Plevani, P., & Muzi-Falconi, M. (2007) · DNA Repair · doi:10.1016/j.dnarep.2006.09.002 · Cited by 65 · see citing works
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Haghnazari, E. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh717 · Cited by 20 · see citing works
Taschner, M., Harreman, M., Teng, Y., Gill, H., Anindya, R., Maslen, S. L., Skehel, J. M., Waters, R., & Svejstrup, J. Q. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00822-09 · Cited by 19 · see citing works
- Authors
- Zhao, X., Muller, E. G. D., & Rothstein, R.
- Affiliations
- Columbia University (US)
- University of Washington (US)
- Corresponding author
- Rothstein, Rodney
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 1998-09
- Volume
- 2
- Issue
- 3
- Pages
- 329-340
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2034206561
- Cited by
- 728
- References
- 54
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 12 · 2023: 14 · 2022: 17 · 2021: 22 · 2020: 20 · 2019: 26 · 2018: 24 · 2017: 38 · 2016: 29 · 2015: 33 · 2014: 26 · 2013: 47 · 2012: 29
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 50237)
- 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 › Molecular Biology › Biochemical and Molecular Research
- Keywords
- RNR1, ribonucleotide reductase, dNTP pools, Mec1, Rad53, DNA damage checkpoint, mitochondrial biogenesis, DNA damage response, cell growth, Saccharomyces cerevisiae
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cloning, Molecular, Deoxyribonucleotides, DNA Damage, DNA Repair, Enzyme Inhibitors, Fungal Proteins, Genes, Fungal, Genes, Lethal, Genetic Complementation Test, Mitochondria, Molecular Sequence Data, Protein Kinases, Ribonucleotide Reductases, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Protein Serine-Threonine Kinases, Gene Deletion, DNA Primers, Cell Cycle Proteins, Genes, Essential, Saccharomyces cerevisiae Proteins, Intracellular Signaling Peptides and Proteins, Checkpoint Kinase 2
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