Genomes and Genes
Gene Symbol: SML1
Description: ribonucleotide reductase inhibiting protein SML1
Alias: ribonucleotide reductase inhibiting protein SML1
Species: Saccharomyces cerevisiae S288c
- Wu X, Huang M. Dif1 controls subcellular localization of ribonucleotide reductase by mediating nuclear import of the R2 subunit. Mol Cell Biol. 2008;28:7156-67 pubmed publisher..Saccharomyces cerevisiae Sml1 binds R1 and inhibits its activity, while Schizosaccharomyces pombe Spd1 impedes RNR holoenzyme formation by ..
- Myung K, Datta A, Kolodner R. Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell. 2001;104:397-408 pubmed..These data suggest that one role of S phase checkpoint functions in normal cells is to suppress spontaneous genome rearrangements resulting from DNA replication errors. ..
- Myung K, Chen C, Kolodner R. Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae. Nature. 2001;411:1073-6 pubmed..Mutations that inactivate these pathways cause high rates of GCRs and show synergistic interactions, indicating that the pathways that suppress GCRs all compete for the same DNA substrates. ..
- Zhao X, Muller E, Rothstein R. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol Cell. 1998;2:329-40 pubmed..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...
- Makovets S, Blackburn E. DNA damage signalling prevents deleterious telomere addition at DNA breaks. Nat Cell Biol. 2009;11:1383-6 pubmed publisher..These findings uncover a new regulatory mechanism that coordinates competing DNA end-processing activities and thereby promotes DNA repair accuracy and genome integrity. ..
- Gunjan A, Verreault A. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. Cell. 2003;115:537-49 pubmed..Our results argue that Rad53 contributes to genome stability independently of Mec1 by preventing the damaging effects of excess histones both during normal cell cycle progression and in response to DNA damage. ..
- Fasullo M, Tsaponina O, Sun M, Chabes A. Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants. Nucleic Acids Res. 2010;38:1195-203 pubmed publisher..All the hyper-recombination phenotypes were reduced by SML1 deletions, which increase dNTP levels...
- Tang H, Siu K, Wong C, Jin D. Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levels. PLoS Genet. 2009;5:e1000697 pubmed publisher..Strong genetic interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1 were found when mutant cells were analyzed for either sensitivity to DNA damage or rate of spontaneous ..
- Zhao X, Rothstein R. The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1. Proc Natl Acad Sci U S A. 2002;99:3746-51 pubmed..In addition, yeast checkpoint proteins Mec1 and Rad53 also regulate the RNR inhibitor Sml1. After DNA damage or at S phase, Mec1 and Rad53 control the phosphorylation and concomitant degradation of Sml1 ..
- Fiorani S, Mimun G, Caleca L, Piccini D, Pellicioli A. Characterization of the activation domain of the Rad53 checkpoint kinase. Cell Cycle. 2008;7:493-9 pubmed..We further found that the protein level of Sml1, which is the physiological inhibitor of ribonucleotide reductase, remains high during DNA replication in rad53-..
- Zhao X, Chabes A, Domkin V, Thelander L, Rothstein R. The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage. EMBO J. 2001;20:3544-53 pubmed..Here we show that their role in growth is to remove the ribonucleotide reductase inhibitor Sml1 to ensure DNA replication. Sml1 protein levels fluctuate during the cell cycle, being lowest during S phase...
- Gangavarapu V, Santa Maria S, Prakash S, Prakash L. Requirement of replication checkpoint protein kinases Mec1/Rad53 for postreplication repair in yeast. MBio. 2011;2:e00079-11 pubmed publisher..We discuss this important issue and suggest that lesion bypass in Saccharomyces cerevisiae cells occurs in conjunction with the stalled replication forks and not in gaps. ..
- Baruffini E, Lodi T, Dallabona C, Puglisi A, Zeviani M, Ferrero I. Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans. Hum Mol Genet. 2006;15:2846-55 pubmed..in yeast, we have overexpressed a dNTP checkpoint enzyme, ribonucleotide reductase, RNR1, or deleted its inhibitor, SML1. In both mutant strains, the petite mutability was dramatically reduced...
- Uchiki T, Dice L, Hettich R, Dealwis C. Identification of phosphorylation sites on the yeast ribonucleotide reductase inhibitor Sml1. J Biol Chem. 2004;279:11293-303 pubmedb>Sml1 is a small protein in Saccharomyces cerevisiae which inhibits the activity of ribonucleotide reductase (RNR). RNR catalyzes the rate-limiting step of de novo dNTP synthesis...
- Tsaponina O, Barsoum E, Aström S, Chabes A. Ixr1 is required for the expression of the ribonucleotide reductase Rnr1 and maintenance of dNTP pools. PLoS Genet. 2011;7:e1002061 pubmed publisher..the activity of ribonucleotide reductase (RNR) by multiple mechanisms, including phosphorylation of RNR inhibitors Sml1 and Dif1. Dun1 also activates DNA-damage-inducible genes by inhibiting the Crt1 transcriptional repressor...
- Branzei D, Sollier J, Liberi G, Zhao X, Maeda D, Seki M, et al. Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell. 2006;127:509-22 pubmed..Our results indicate that Ubc9- and Mms21-mediated sumoylation functions as a regulatory mechanism, different from that of replication checkpoints, to prevent pathological accumulation of cruciform structures at damaged forks. ..
- Clerici M, Paciotti V, Baldo V, Romano M, Lucchini G, Longhese M. Hyperactivation of the yeast DNA damage checkpoint by TEL1 and DDC2 overexpression. EMBO J. 2001;20:6485-98 pubmed..In addition, Tel1 overproduction results in transient nuclear division arrest and concomitant Rad53 phosphorylation in the absence of exogenous DNA damage independently of Mec1 and Ddc1. ..
- Banerjee S, Myung K. Increased genome instability and telomere length in the elg1-deficient Saccharomyces cerevisiae mutant are regulated by S-phase checkpoints. Eukaryot Cell. 2004;3:1557-66 pubmed
- Paciotti V, Clerici M, Lucchini G, Longhese M. The checkpoint protein Ddc2, functionally related to S. pombe Rad26, interacts with Mec1 and is regulated by Mec1-dependent phosphorylation in budding yeast. Genes Dev. 2000;14:2046-59 pubmed..Our findings suggest that Ddc2 may be the functional homolog of Schizosaccharomyces pombe Rad26, strengthening the hypothesis that the mechanisms leading to checkpoint activation are conserved throughout evolution. ..
- Schmidt K, Wu J, Kolodner R. Control of translocations between highly diverged genes by Sgs1, the Saccharomyces cerevisiae homolog of the Bloom's syndrome protein. Mol Cell Biol. 2006;26:5406-20 pubmed..The translocation structures observed suggest involvement of a dicentric intermediate and break-induced replication with multiple cycles of DNA template switching. ..
- Koepp D, Kile A, Swaminathan S, Rodriguez Rivera V. The F-box protein Dia2 regulates DNA replication. Mol Biol Cell. 2006;17:1540-8 pubmed..Interestingly, prolonging G1-phase in dia2 cells prevents the accumulation of DNA damage in S-phase. We propose that Dia2 is an origin-binding protein that plays a role in regulating DNA replication. ..
- Bessler J, Zakian V. The amino terminus of the Saccharomyces cerevisiae DNA helicase Rrm3p modulates protein function altering replication and checkpoint activity. Genetics. 2004;168:1205-18 pubmed..These data demonstrate that the amino terminus of Rrm3p is essential for Rrm3p function. However, the helicase domain of Rrm3p also contributes to its functional specificity. ..
- Hoch N, Chen E, Buckland R, Wang S, Fazio A, Hammet A, et al. Molecular basis of the essential s phase function of the rad53 checkpoint kinase. Mol Cell Biol. 2013;33:3202-13 pubmed publisher..Our findings indicate that the essential S phase function of Rad53 is comprised by the combination of its role in regulating basal dNTP levels and its compensatory kinase function if dNTP levels are perturbed. ..
- Kwan E, Foss E, Kruglyak L, Bedalov A. Natural polymorphism in BUL2 links cellular amino acid availability with chronological aging and telomere maintenance in yeast. PLoS Genet. 2011;7:e1002250 pubmed publisher..Identification of a polymorphism in BUL2 in this outbred yeast population revealed a link among cellular amino acid availability, chronological lifespan, and telomere length control. ..
- Fiorani P, Reid R, Schepis A, Jacquiau H, Guo H, Thimmaiah P, et al. The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisons. J Biol Chem. 2004;279:21271-81 pubmed..Additional studies suggest a role for Doa4p in the Rad9p checkpoint response to Top1p poisons. These findings indicate a functional link between ubiquitin-mediated proteolysis and cellular resistance to CPT-induced DNA damage. ..
- Uchiki T, Hettich R, Gupta V, Dealwis C. Characterization of monomeric and dimeric forms of recombinant Sml1p-histag protein by electrospray mass spectrometry. Anal Biochem. 2002;301:35-48 pubmed
- Zhang Z, Yang K, Chen C, Feser J, Huang M. Role of the C terminus of the ribonucleotide reductase large subunit in enzyme regeneration and its inhibition by Sml1. Proc Natl Acad Sci U S A. 2007;104:2217-22 pubmed..The Sml1 protein inhibits ribonucleotide reductase activity by binding to the R1 subunit...
- Jay K, Smith D, Blackburn E. Early Loss of Telomerase Action in Yeast Creates a Dependence on the DNA Damage Response Adaptor Proteins. Mol Cell Biol. 2016;36:1908-19 pubmed publisher..in wild-type cells but showed genetic dependencies distinct from such damage and was completely alleviated by SML1 deletion, which increases deoxynucleoside triphosphate (dNTP) pools...
- Clausing E, Mayer A, Chanarat S, Muller B, Germann S, Cramer P, et al. The transcription elongation factor Bur1-Bur2 interacts with replication protein A and maintains genome stability during replication stress. J Biol Chem. 2010;285:41665-74 pubmed publisher..The transcription elongation factor Bur1-Bur2 interacts with RPA and maintains genome integrity during DNA replication stress. ..
- Biswas D, Takahata S, Xin H, Dutta Biswas R, Yu Y, Formosa T, et al. A role for Chd1 and Set2 in negatively regulating DNA replication in Saccharomyces cerevisiae. Genetics. 2008;178:649-59 pubmed publisher..caused by disruption of either MEC1 or RAD53 DNA damage checkpoint genes, as well as the lethality seen when a mec1 sml1 mutant is exposed to low levels of HU...
- Fasullo M, Dong Z, Sun M, Zeng L. Saccharomyces cerevisiae RAD53 (CHK2) but not CHK1 is required for double-strand break-initiated SCE and DNA damage-associated SCE after exposure to X rays and chemical agents. DNA Repair (Amst). 2005;4:1240-51 pubmed..rad53 sml1 diploid mutants exhibited a 10-fold higher rate of spontaneous translocations compared to the sml1 diploid mutants...
- Karumbati A, Wilson T. Abrogation of the Chk1-Pds1 checkpoint leads to tolerance of persistent single-strand breaks in Saccharomyces cerevisiae. Genetics. 2005;169:1833-44 pubmed..We propose a model in which recombinational repair during S phase coupled with failure of the metaphase-anaphase checkpoint allows for tolerance of persistent single-strand breaks at the expense of genome stability. ..
- Corda Y, Lee S, Guillot S, Walther A, Sollier J, Arbel Eden A, et al. Inactivation of Ku-mediated end joining suppresses mec1Delta lethality by depleting the ribonucleotide reductase inhibitor Sml1 through a pathway controlled by Tel1 kinase and the Mre11 complex. Mol Cell Biol. 2005;25:10652-64 pubmed..We further report that this Mec1-independent pathway converges with the Rad53/Dun1-regulated checkpoint kinase cascade and leads to the degradation of the ribonucleotide reductase inhibitor Sml1.
- Myung K, Kolodner R. Suppression of genome instability by redundant S-phase checkpoint pathways in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2002;99:4500-7 pubmed..These data support the view that spontaneous genome rearrangements result from DNA replication errors and indicate that there is a high degree of redundancy among the checkpoints that act in S phase to suppress such genome instability. ..
- Rouse J, Jackson S. LCD1: an essential gene involved in checkpoint control and regulation of the MEC1 signalling pathway in Saccharomyces cerevisiae. EMBO J. 2000;19:5801-12 pubmed..These results indicate that Lcd1p is a pivotal checkpoint regulator, involved in both the essential and checkpoint functions of the Mec1p pathway. ..
- Nguyen V, Clelland B, Hockman D, Kujat Choy S, Mewhort H, Schultz M. Replication stress checkpoint signaling controls tRNA gene transcription. Nat Struct Mol Biol. 2010;17:976-81 pubmed publisher..We propose that checkpoint control of the fork-pausing activity of tRNA genes complements the repertoire of replisome-targeted mechanisms by which checkpoint proteins promote faithful DNA replication. ..
- Edenberg E, Vashisht A, Benanti J, Wohlschlegel J, Toczyski D. Rad53 downregulates mitotic gene transcription by inhibiting the transcriptional activator Ndd1. Mol Cell Biol. 2014;34:725-38 pubmed publisher..Finally, we show that downregulation of Ndd1 is an essential function of Rad53, as a hypomorphic ndd1 allele rescues RAD53 deletion. ..
- Crider D, García Rodríguez L, Srivastava P, Peraza Reyes L, Upadhyaya K, Boldogh I, et al. Rad53 is essential for a mitochondrial DNA inheritance checkpoint regulating G1 to S progression. J Cell Biol. 2012;198:793-8 pubmed publisher..These findings support the existence of a Rad53p-regulated checkpoint that regulates G1- to S-phase progression in response to loss of mtDNA. ..
- Ju D, Wang X, Ha S, Fu J, Xie Y. Inhibition of proteasomal degradation of rpn4 impairs nonhomologous end-joining repair of DNA double-strand breaks. PLoS ONE. 2010;5:e9877 pubmed publisher..Inhibition of Rpn4 degradation may result in a concomitant delay of release of Rpn4 and the proteasome from a DSB. This study provides the first evidence for the role of proteasomal degradation of Rpn4 in NHEJ. ..
- Burgess R, Zhou H, Han J, Zhang Z. A role for Gcn5 in replication-coupled nucleosome assembly. Mol Cell. 2010;37:469-80 pubmed publisher..These results demonstrate that Gcn5 regulates RC nucleosome assembly, in part, by promoting H3 association with CAF-1 via H3 acetylation. ..
- Taschner M, Harreman M, Teng Y, Gill H, Anindya R, Maslen S, et al. A role for checkpoint kinase-dependent Rad26 phosphorylation in transcription-coupled DNA repair in Saccharomyces cerevisiae. Mol Cell Biol. 2010;30:436-46 pubmed publisher..These findings establish a direct role for Mec1 kinase in transcription-coupled repair, at least partly via phosphorylation of Rad26, the main transcription-repair coupling factor. ..
- Gómez González B, Felipe Abrio I, Aguilera A. The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants. Mol Cell Biol. 2009;29:5203-13 pubmed publisher..In light of these results, we propose a model in which R-loop-mediated recombination is explained by template switching. ..
- Felipe Abrio I, Lafuente Barquero J, GarcÃa Rubio M, Aguilera A. RNA polymerase II contributes to preventing transcription-mediated replication fork stalls. EMBO J. 2015;34:236-50 pubmed publisher..Our results imply that the RNAPII or ancillary factors actively help prevent transcription-associated genome instability. ..
- Nagai S, Dubrana K, Tsai Pflugfelder M, Davidson M, Roberts T, Brown G, et al. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science. 2008;322:597-602 pubmed publisher..This suggests that strand breaks are shunted to nuclear pores for a repair pathway controlled by a conserved SUMO-dependent E3 ligase. ..
- Marsolier M, Roussel P, Leroy C, Mann C. Involvement of the PP2C-like phosphatase Ptc2p in the DNA checkpoint pathways of Saccharomyces cerevisiae. Genetics. 2000;154:1523-32 pubmed..Deleting PTC2 specifically suppresses the hydroxyurea hypersensitivity of mec1 mutants and the lethality of mec1Delta. PTC2 is thus implicated in one or several functions related to RAD53, MEC1, and the DNA checkpoint pathways. ..
- Nakada D, Hirano Y, Sugimoto K. Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway. Mol Cell Biol. 2004;24:10016-25 pubmed..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. ..
- Manfrini N, Gobbini E, Baldo V, Trovesi C, Lucchini G, Longhese M. G(1)/S and G(2)/M cyclin-dependent kinase activities commit cells to death in the absence of the S-phase checkpoint. Mol Cell Biol. 2012;32:4971-85 pubmed publisher..Moreover, these findings suggest that the essential function of Mec1 and Rad53 is not necessarily separated from the function of these kinases in supporting DNA synthesis under stress conditions. ..
- Au T, Rodriguez J, Vincent J, Tsukiyama T. ATP-dependent chromatin remodeling factors tune S phase checkpoint activity. Mol Cell Biol. 2011;31:4454-63 pubmed publisher..Based on these results, we propose that Isw2 and Ino80 are targeted to stalled replication forks via RPA and directly control the amplitude of S phase checkpoint activity and the subsequent deactivation process. ..
- Williams L, Marjavaara L, Knowels G, Schultz E, Fox E, Chabes A, et al. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ? variants. Proc Natl Acad Sci U S A. 2015;112:E2457-66 pubmed publisher..Thus, dNTP pool levels correlate with Pol ? mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy. ..
- Pawar V, Jingjing L, Patel N, Kaur N, Doetsch P, Shadel G, et al. Checkpoint kinase phosphorylation in response to endogenous oxidative DNA damage in repair-deficient stationary-phase Saccharomyces cerevisiae. Mech Ageing Dev. 2009;130:501-8 pubmed publisher..Single-strand resection may be accelerated by unrepaired oxidative base damage in the vicinity of a double-strand break. ..
- Misko T, Wijerathna S, Radivoyevitch T, Berdis A, Ahmad M, Harris M, et al. Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme. FEBS Lett. 2016;590:1704-12 pubmed publisherb>Sml1 is an intrinsically disordered protein inhibitor of Saccharomyces cerevisiae ribonucleotide reductase (ScRR1), but its inhibition mechanism is poorly understood...
- Clerici M, Trovesi C, Galbiati A, Lucchini G, Longhese M. Mec1/ATR regulates the generation of single-stranded DNA that attenuates Tel1/ATM signaling at DNA ends. EMBO J. 2014;33:198-216 pubmed publisher..Thus, Mec1 regulates the generation of ssDNA at DSBs, and this control is important to coordinate Mec1 and Tel1 signaling activities at these breaks. ..
- Schramke V, Neecke H, Brevet V, Corda Y, Lucchini G, Longhese M, et al. The set1Delta mutation unveils a novel signaling pathway relayed by the Rad53-dependent hyperphosphorylation of replication protein A that leads to transcriptional activation of repair genes. Genes Dev. 2001;15:1845-58 pubmed
- Dubrana K, van Attikum H, Hediger F, Gasser S. The processing of double-strand breaks and binding of single-strand-binding proteins RPA and Rad51 modulate the formation of ATR-kinase foci in yeast. J Cell Sci. 2007;120:4209-20 pubmed..These observations led to a model that links end-processing and competition between different ssDNA-binding factors with Mec1-Ddc2 focus formation and checkpoint activation. ..
- Li J, Coïc E, Lee K, Lee C, Kim J, Wu Q, et al. Regulation of budding yeast mating-type switching donor preference by the FHA domain of Fkh1. PLoS Genet. 2012;8:e1002630 pubmed publisher..We also find that when RE binds to the region near the DSB at MATa then Mec1 and Tel1 checkpoint kinases are not only able to phosphorylate histone H2A (?-H2AX) around the DSB but can also promote ?-H2AX spreading around the RE region. ..
- Lopez Mosqueda J, Maas N, Jonsson Z, Defazio Eli L, Wohlschlegel J, Toczyski D. Damage-induced phosphorylation of Sld3 is important to block late origin firing. Nature. 2010;467:479-83 pubmed publisher..These data indicate that the intra-S-phase checkpoint functions to block late origin firing in adverse conditions to prevent genomic instability and maximize cell survival. ..
- Sharp J, Rizki G, Kaufman P. Regulation of histone deposition proteins Asf1/Hir1 by multiple DNA damage checkpoint kinases in Saccharomyces cerevisiae. Genetics. 2005;171:885-99 pubmed..We conclude that the Mec1 and Dun1 checkpoint kinases regulate the Asf1-Rad53 interaction and therefore affect the activity of the Asf1/Hir complex in vivo. ..
- Ivessa A, Lenzmeier B, Bessler J, Goudsouzian L, Schnakenberg S, Zakian V. The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes. Mol Cell. 2003;12:1525-36 pubmed..These data indicate that the Rrm3p DNA helicase helps replication forks traverse protein-DNA complexes, naturally occurring impediments that are encountered in each S phase. ..
- Sanvisens N, Romero A, An X, Zhang C, de Llanos R, Martínez Pastor M, et al. Yeast Dun1 kinase regulates ribonucleotide reductase inhibitor Sml1 in response to iron deficiency. Mol Cell Biol. 2014;34:3259-71 pubmed publisher..We show here that the levels of the Sml1 protein, a yeast RNR large-subunit inhibitor, specifically decrease in response to both nutritional and genetic Fe ..
- Hammet A, Pike B, Heierhorst J. Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1 kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication blocks. J Biol Chem. 2002;277:22469-74 pubmed..deoxyribonucleotide levels as it was also observed in strains lacking the ribonucleotide reductase inhibitor Sml1. dun1pan2 mutants initially arrested normally in response to replication blocks but died in the presence of ..
- Danielsson J, Liljedahl L, Bárány Wallje E, Sønderby P, Kristensen L, Martinez Yamout M, et al. The intrinsically disordered RNR inhibitor Sml1 is a dynamic dimer. Biochemistry. 2008;47:13428-37 pubmedb>Sml1 is a small ribonucleotide reductase (RNR) regulatory protein in Saccharomyces cerevisiae that binds to and inhibits RNR activation...
- Azad G, Singh V, Golla U, Tomar R. Depletion of cellular iron by curcumin leads to alteration in histone acetylation and degradation of Sml1p in Saccharomyces cerevisiae. PLoS ONE. 2013;8:e59003 pubmed publisher..These findings suggest that the medicinal properties of curcumin are largely contributed by its cumulative effect of iron starvation and epigenetic modifications. ..
- Carlborg K, Kanno T, Carter S, SjÃ¶gren C. Mec1-dependent phosphorylation of Mms21 modulates its SUMO ligase activity. DNA Repair (Amst). 2015;28:83-92 pubmed publisher..We propose that one function of S260 S261 phosphorylation is to positively regulate the SUMO ligase activity of Mms21 and thereby promote genomic stability. ..
- Caldwell J, Chen Y, Schollaert K, Theis J, Babcock G, Newlon C, et al. Orchestration of the S-phase and DNA damage checkpoint pathways by replication forks from early origins. J Cell Biol. 2008;180:1073-86 pubmed publisher..Thus, oncogene-mediated deregulation of cyclins in the early stages of cancer development could contribute to genomic instability through a deficiency in the forks required to establish the S-phase checkpoint. ..