RAD53

Summary

Gene Symbol: RAD53
Description: serine/threonine/tyrosine protein kinase RAD53
Alias: LSD1, MEC2, SPK1, serine/threonine/tyrosine protein kinase RAD53
Species: Saccharomyces cerevisiae S288c
Products:     RAD53

Top Publications

  1. Zheng P, Fay D, Burton J, Xiao H, Pinkham J, Stern D. SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase. Mol Cell Biol. 1993;13:5829-42 pubmed
    b>SPK1 was originally discovered in an immunoscreen for tyrosine-protein kinases in Saccharomyces cerevisiae. We have used biochemical and genetic techniques to investigate the function of this gene and its encoded protein...
  2. Weinert T, Kiser G, Hartwell L. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev. 1994;8:652-65 pubmed
    ..The MEC2 gene proves to be identical to the RAD53 gene...
  3. 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 Saccharomyces cerevisiae Dun1 protein kinase is a downstream target of the conserved Mec1-Rad53 checkpoint pathway...
  4. 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
    b>Rad53 protein, the yeast orthologue of the human checkpoint kinase Chk2, presents two highly conserved phosphorylatable threonine residues (T354 and T358) in the activation domain, whose phosphorylation is critical to allow the ..
  5. de Bruin R, Kalashnikova T, Chahwan C, McDonald W, Wohlschlegel J, Yates J, et al. Constraining G1-specific transcription to late G1 phase: the MBF-associated corepressor Nrm1 acts via negative feedback. Mol Cell. 2006;23:483-96 pubmed
    ..In both yeasts, MBF represses G1-specific transcription outside of G1 phase. A negative feedback loop involving Nrm1 bound to MBF leads to transcriptional repression as cells exit G1 phase. ..
  6. Matthews L, Jones D, Prasad A, Duncker B, Guarné A. Saccharomyces cerevisiae Dbf4 has unique fold necessary for interaction with Rad53 kinase. J Biol Chem. 2012;287:2378-87 pubmed publisher
    ..During the replication checkpoint, Saccharomyces cerevisiae Dbf4 is phosphorylated in a Rad53-dependent manner, and this, in turn, inhibits initiation of replication at late origins...
  7. Torres J, Schnakenberg S, Zakian V. Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities. Mol Cell Biol. 2004;24:3198-212 pubmed
    ..The rrm3 system provides a unique opportunity to learn the fate of forks whose progress is impaired by natural impediments rather than by exogenous DNA damage. ..
  8. Gilbert C, Green C, Lowndes N. Budding yeast Rad9 is an ATP-dependent Rad53 activating machine. Mol Cell. 2001;8:129-36 pubmed
    ..Rad9, whereas the smaller (560 kDa) complex, which forms after DNA damage, contains hyperphosphorylated Rad9 and Rad53. This smaller Rad9 complex is capable of catalyzing phosphorylation and release of active Rad53 kinase, a process ..
  9. 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
    The essential yeast kinases Mec1 and Rad53, or human ATR and Chk1, are crucial for checkpoint responses to exogenous genotoxic agents, but why they are also required for DNA replication in unperturbed cells remains poorly understood...

More Information

Publications85

  1. Majka J, Niedziela Majka A, Burgers P. The checkpoint clamp activates Mec1 kinase during initiation of the DNA damage checkpoint. Mol Cell. 2006;24:891-901 pubmed
    ..of the clamp in regulating Mec1, and we delineate how the signal generated by DNA lesions is transduced to the Rad53 effector kinase...
  2. Dohrmann P, Sclafani R. Novel role for checkpoint Rad53 protein kinase in the initiation of chromosomal DNA replication in Saccharomyces cerevisiae. Genetics. 2006;174:87-99 pubmed
    A novel role for Rad53 in the initiation of DNA replication that is independent of checkpoint or deoxynucleotide regulation is proposed...
  3. Naiki T, Wakayama T, Nakada D, Matsumoto K, Sugimoto K. Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism. Mol Cell Biol. 2004;24:3277-85 pubmed
    ..Rad9 is phosphorylated after DNA damage in a Mec1- and Tel1-dependent manner and subsequently interacts with Rad53. This Rad9-Rad53 interaction has been suggested to trigger the activation and phosphorylation of Rad53...
  4. Weinreich M, Stillman B. Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway. EMBO J. 1999;18:5334-46 pubmed
    ..The Dbf4p phosphorylation in response to HU is RAD53 dependent. This suggests that an S-phase checkpoint function regulates Cdc7p-Dbf4p kinase activity...
  5. 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
    ..The Mec1/Rad53-dependent replication checkpoint plays a crucial role in the maintenance of stable and functional replication ..
  6. 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. ..
  7. 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
    ..mutants display replication fork progression impairment at actively transcribed chromosomal regions and trigger Rad53 phosphorylation...
  8. Herzberg K, Bashkirov V, Rolfsmeier M, Haghnazari E, McDonald W, Anderson S, et al. Phosphorylation of Rad55 on serines 2, 8, and 14 is required for efficient homologous recombination in the recovery of stalled replication forks. Mol Cell Biol. 2006;26:8396-409 pubmed
    ..These results suggest that Rad55-S2,8,14 phosphorylation activates recombinational repair, allowing for faster recovery after genotoxic stress. ..
  9. Pellicioli A, Lee S, Lucca C, Foiani M, Haber J. Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol Cell. 2001;7:293-300 pubmed
    ..We conclude that activation of the checkpoint kinases in response to a single DNA break is cell cycle regulated and that adaptation is an active process by which these kinases are inactivated. ..
  10. Emili A. MEC1-dependent phosphorylation of Rad9p in response to DNA damage. Mol Cell. 1998;2:183-9 pubmed
    In budding yeast, DNA damage can activate a checkpoint surveillance system controlled by the RAD9, RAD53, and MEC1 genes, resulting in a delay in cell cycle progression...
  11. Ma J, Lee S, Duong J, Stern D. Activation of the checkpoint kinase Rad53 by the phosphatidyl inositol kinase-like kinase Mec1. J Biol Chem. 2006;281:3954-63 pubmed
    Saccharomyces cerevisiae Rad53, the ortholog of mammalian Chk2, is an essential protein kinase in DNA damage and DNA replication checkpoint pathways...
  12. Frei C, Gasser S. The yeast Sgs1p helicase acts upstream of Rad53p in the DNA replication checkpoint and colocalizes with Rad53p in S-phase-specific foci. Genes Dev. 2000;14:81-96 pubmed
    ..The association of Rad53p with a chromatin subfraction is Sgs1p dependent, suggesting an important role for the helicase in the signal-transducing pathway that monitors replication fork progression. ..
  13. Hegnauer A, Hustedt N, Shimada K, Pike B, Vogel M, Amsler P, et al. An N-terminal acidic region of Sgs1 interacts with Rpa70 and recruits Rad53 kinase to stalled forks. EMBO J. 2012;31:3768-83 pubmed publisher
    ..However, the Sgs1 R1 domain is a target of Mec1 kinase, deletion of which compromises Rad53 activation on HU...
  14. Chen S, Smolka M, Zhou H. Mechanism of Dun1 activation by Rad53 phosphorylation in Saccharomyces cerevisiae. J Biol Chem. 2007;282:986-95 pubmed
    ..Using this assay, we confirmed the genetic basis of Dun1 activation. Rad53 was found to be directly responsible for Dun1 activation...
  15. Guillemain G, Ma E, Mauger S, Miron S, Thai R, Guerois R, et al. Mechanisms of checkpoint kinase Rad53 inactivation after a double-strand break in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:3378-89 pubmed
    ..type are required for DNA checkpoint inactivation after a DSB and probably dephosphorylate the checkpoint kinase Rad53. In this article we have investigated further the interactions between Ptc2 and Rad53...
  16. Neecke H, Lucchini G, Longhese M. Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1- and Rad53-dependent checkpoint in budding yeast. EMBO J. 1999;18:4485-97 pubmed
    ..In fact, Mec1 and Rad53, but not Rad9 and the Rad24 group of checkpoint proteins, are required to delay cell cycle progression in ..
  17. 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
    ..firing of late replicating origins, and this inhibition requires both Mec1 and the downstream checkpoint kinase Rad53 (Chk2 in humans)...
  18. Schwartz M, Duong J, Sun Z, Morrow J, Pradhan D, Stern D. Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Mol Cell. 2002;9:1055-65 pubmed
    ..for the MEC1/TEL1-dependent activation of Saccharomyces cerevisiae DNA damage checkpoint pathways mediated by Rad53 and Chk1. DNA damage induces Rad9 phosphorylation, and Rad53 specifically associates with phosphorylated Rad9...
  19. Chen S, Zhou H. Reconstitution of Rad53 activation by Mec1 through adaptor protein Mrc1. J Biol Chem. 2009;284:18593-604 pubmed publisher
    ..Activation of Rad53, a key effector kinase in the budding yeast Saccharomyces cerevisiae, is essential for stabilizing DNA replication ..
  20. Smolka M, Albuquerque C, Chen S, Zhou H. Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proc Natl Acad Sci U S A. 2007;104:10364-9 pubmed
    ..phosphoproteomics to identify in vivo kinase substrates of the yeast DNA damage checkpoint kinases Mec1, Tel1, and Rad53 (orthologs of human ATR, ATM, and CHK2, respectively)...
  21. Blankley R, Lydall D. A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J Cell Sci. 2004;117:601-8 pubmed
    ..is to link the activity of the Mec1 kinase to the activation of two parallel signalling pathways dependent on the Rad53 and Chk1 kinases. The mechanisms by which Rad9 interacts with, and activates, Rad53 are well understood...
  22. Berens T, Toczyski D. Colocalization of Mec1 and Mrc1 is sufficient for Rad53 phosphorylation in vivo. Mol Biol Cell. 2012;23:1058-67 pubmed publisher
    ..an in vivo replication-checkpoint mimic that recapitulates Mec1-dependent phosphorylation of the effector kinase Rad53, a crucial step in checkpoint activation...
  23. Schleker T, Shimada K, Sack R, Pike B, Gasser S. Cell cycle-dependent phosphorylation of Rad53 kinase by Cdc5 and Cdc28 modulates checkpoint adaptation. Cell Cycle. 2010;9:350-63 pubmed
    ..Specifically, higher amounts of damage are needed to activate the downstream checkpoint kinase Rad53 in S-phase cells...
  24. Emili A, Schieltz D, Yates J, Hartwell L. Dynamic interaction of DNA damage checkpoint protein Rad53 with chromatin assembly factor Asf1. Mol Cell. 2001;7:13-20 pubmed
    The evolutionarily conserved yeast checkpoint protein kinase Rad53 regulates cell cycle progression, transcription, and DNA repair in response to DNA damage...
  25. Usui T, Foster S, Petrini J. Maintenance of the DNA-damage checkpoint requires DNA-damage-induced mediator protein oligomerization. Mol Cell. 2009;33:147-59 pubmed publisher
    ..b>Rad53 activation is unaffected by mutations that impair Rad9 oligomerization, but checkpoint maintenance is lost, ..
  26. Conde F, Ontoso D, Acosta I, Gallego Sánchez A, Bueno A, San Segundo P. Regulation of tolerance to DNA alkylating damage by Dot1 and Rad53 in Saccharomyces cerevisiae. DNA Repair (Amst). 2010;9:1038-49 pubmed publisher
    ..Here, we investigate the functional contribution of the Dot1 histone methyltransferase and the Rad53 checkpoint kinase to TLS regulation in Saccharomyces cerevisiae...
  27. Bashkirov V, Bashkirova E, Haghnazari E, Heyer W. Direct kinase-to-kinase signaling mediated by the FHA phosphoprotein recognition domain of the Dun1 DNA damage checkpoint kinase. Mol Cell Biol. 2003;23:1441-52 pubmed
    ..It belongs to the Chk2 family of checkpoint kinases, which includes S. cerevisiae Rad53 and Mek1, Schizosaccharomyces pombe Cds1, and human Chk2...
  28. 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
    The evolutionarily conserved protein kinases Mec1 and Rad53 are required for checkpoint response and growth. Here we show that their role in growth is to remove the ribonucleotide reductase inhibitor Sml1 to ensure DNA replication...
  29. Lee S, Duong J, Stern D. A Ddc2-Rad53 fusion protein can bypass the requirements for RAD9 and MRC1 in Rad53 activation. Mol Biol Cell. 2004;15:5443-55 pubmed
    ..In addition, expression of Ddc2-Rad53p in Deltarad24Deltarad17Deltamec3 cells increased cell survival. These results reveal minimal requirements for function of a core checkpoint signaling system. ..
  30. 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
    ..Mutations in Saccharomyces cerevisiae RFC5, DPB11, MEC1, DDC2 MEC3, RAD53, CHK1, PDS1, and DUN1 increased the rate of genome rearrangements up to 200-fold whereas mutations in RAD9, RAD17, ..
  31. Desany B, Alcasabas A, Bachant J, Elledge S. Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Genes Dev. 1998;12:2956-70 pubmed
    b>RAD53 and MEC1 are essential genes required for the transcriptional and cell cycle responses to DNA damage and DNA replication blocks...
  32. Feng W, Bachant J, Collingwood D, Raghuraman M, Brewer B. Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress. Genetics. 2009;183:1249-60 pubmed publisher
    ..different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes...
  33. Bjergbaek L, Cobb J, Tsai Pflugfelder M, Gasser S. Mechanistically distinct roles for Sgs1p in checkpoint activation and replication fork maintenance. EMBO J. 2005;24:405-17 pubmed
  34. Segurado M, Diffley J. Separate roles for the DNA damage checkpoint protein kinases in stabilizing DNA replication forks. Genes Dev. 2008;22:1816-27 pubmed publisher
    ..In budding yeast, the protein kinases Mec1 (ATR) and Rad53 (Chk2) are especially important in this process...
  35. O Neill B, Szyjka S, Lis E, Bailey A, Yates J, Aparicio O, et al. Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage. Proc Natl Acad Sci U S A. 2007;104:9290-5 pubmed
    Activation of the checkpoint kinase Rad53 is a critical response to DNA damage that results in stabilization of stalled replication forks, inhibition of late-origin initiation, up-regulation of dNTP levels, and delayed entry to mitosis...
  36. Leroy C, Lee S, Vaze M, Ochsenbein F, Ochsenbien F, Guerois R, et al. PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break. Mol Cell. 2003;11:827-35 pubmed
    ..In vivo and in vitro evidence suggests that phosphorylated forms of Ptc2 and Ptc3 specifically bind to the Rad53 FHA1 domain and inactivate Rad53-dependent pathways during adaptation and recovery by dephosphorylating Rad53.
  37. Duncker B, Shimada K, Tsai Pflugfelder M, Pasero P, Gasser S. An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing. Proc Natl Acad Sci U S A. 2002;99:16087-92 pubmed
    ..Given that the activation of Rad53 kinase in response to the DNA replication checkpoint leads to the release of Dbf4p from an ORC-containing ..
  38. Sun Z, Hsiao J, Fay D, Stern D. Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Science. 1998;281:272-4 pubmed
    The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA...
  39. Gunjan A, Verreault A. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. Cell. 2003;115:537-49 pubmed
    b>Rad53 and Mec1 are protein kinases required for DNA replication and recovery from DNA damage in Saccharomyces cerevisiae...
  40. 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 both yeast and humans, RNR is transcriptionally induced after DNA damage via Mec1/Rad53 (yeast) and ATM/CHK2 (human) checkpoint pathways...
  41. Sweeney F, Yang F, Chi A, Shabanowitz J, Hunt D, Durocher D. Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Curr Biol. 2005;15:1364-75 pubmed
    ..To elucidate the mechanisms that underlie the MEC1 and RAD9-dependent activation of Rad53, the Saccharomyces cerevisiae ortholog of Chk2, we mapped and characterized in vivo phosphorylation sites present ..
  42. 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
    ..Specifically, the sensor kinase Mec1, the signaling adaptor Mrc1 and the transducer kinase Rad53 relay signals that globally repress tRNA gene transcription during unchallenged proliferation and under conditions ..
  43. Kim H, Vijayakumar S, Reger M, Harrison J, Haber J, Weil C, et al. Functional interactions between Sae2 and the Mre11 complex. Genetics. 2008;178:711-23 pubmed publisher
    ..We show that Sae2 oligomerizes independently of DNA damage and that oligomerization is required for its regulatory influence on the Mre11 nuclease and checkpoint functions. ..
  44. Reis C, Campbell J. Contribution of Trf4/5 and the nuclear exosome to genome stability through regulation of histone mRNA levels in Saccharomyces cerevisiae. Genetics. 2007;175:993-1010 pubmed
    ..find that TRF4 shows synthetic genetic interactions with genes that negatively regulate histone levels, including RAD53. Moreover, synthetic lethality of trf4Delta rad53Delta is rescued by reducing histone levels whereas ..
  45. Szyjka S, Aparicio J, Viggiani C, Knott S, Xu W, Tavare S, et al. Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae. Genes Dev. 2008;22:1906-20 pubmed publisher
    Replication fork stalling at a DNA lesion generates a damage signal that activates the Rad53 kinase, which plays a vital role in survival by stabilizing stalled replication forks...
  46. Chen Y, Kenworthy J, Gabrielse C, Hänni C, Zegerman P, Weinreich M. DNA replication checkpoint signaling depends on a Rad53-Dbf4 N-terminal interaction in Saccharomyces cerevisiae. Genetics. 2013;194:389-401 pubmed publisher
    ..b>Rad53 kinase is a central effector of the replication checkpoint and both binds to and phosphorylates Dbf4 to prevent ..
  47. Usui T, Petrini J. The Saccharomyces cerevisiae 14-3-3 proteins Bmh1 and Bmh2 directly influence the DNA damage-dependent functions of Rad53. Proc Natl Acad Sci U S A. 2007;104:2797-802 pubmed
    In this study, we mutated autophosphorylation sites in Rad53 based on their conservation with previously identified autophosphorylation sites in the mammalian Rad53 ortholog, Chk2...
  48. Ghavidel A, Kislinger T, Pogoutse O, Sopko R, Jurisica I, Emili A. Impaired tRNA nuclear export links DNA damage and cell-cycle checkpoint. Cell. 2007;131:915-26 pubmed
    ..This response requires an intact MEC1- and RAD53-dependent signaling pathway that impedes the nuclear export of intron-containing tRNA via differential ..
  49. Vialard J, Gilbert C, Green C, Lowndes N. The budding yeast Rad9 checkpoint protein is subjected to Mec1/Tel1-dependent hyperphosphorylation and interacts with Rad53 after DNA damage. EMBO J. 1998;17:5679-88 pubmed
    ..Analysis of checkpoint protein interactions after DNA damage revealed that Rad9 physically associates with Rad53.
  50. Barbour L, Ball L, Zhang K, Xiao W. DNA damage checkpoints are involved in postreplication repair. Genetics. 2006;174:1789-800 pubmed
    ..These results suggest that a damage checkpoint is essential for tolerance mediated by both the error-free and error-prone branches of PRR. ..
  51. Singh R, Kabbaj M, Paik J, Gunjan A. Histone levels are regulated by phosphorylation and ubiquitylation-dependent proteolysis. Nat Cell Biol. 2009;11:925-33 pubmed publisher
    ..Although chromosomal histones are stable, excess (non-chromatin bound) histones are rapidly degraded in a Rad53 (radiation sensitive 53) kinase-dependent manner in Saccharomyces cerevisiae...
  52. Kumar S, Burgers P. Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery. Genes Dev. 2013;27:313-21 pubmed publisher
    ..cerevisiae Ddc1-Mec3-Rad17 and human Rad9-Rad1-Hus1) and Dpb11, the ortholog of human TopBP1. A triple mutant that eliminates the checkpoint functions of all three initiators abrogates the Mec1-dependent checkpoint. ..
  53. Sidorova J, Breeden L. Rad53-dependent phosphorylation of Swi6 and down-regulation of CLN1 and CLN2 transcription occur in response to DNA damage in Saccharomyces cerevisiae. Genes Dev. 1997;11:3032-45 pubmed
    ..We have shown that after a pulse of DNA damage in G1 with the alkylating agent MMS, there is also a MEC1-, RAD53-, and RAD9-dependent delay in G1...
  54. Gabrielse C, Miller C, McConnell K, DeWard A, Fox C, Weinreich M. A Dbf4p BRCA1 C-terminal-like domain required for the response to replication fork arrest in budding yeast. Genetics. 2006;173:541-55 pubmed
    ..Rad53p likely directly phosphorylated Dbf4p in response to RF arrest and Dbf4p was required for Rad53p abundance. Rad53p and Dbf4p therefore cooperated to coordinate a robust cellular response to RF arrest. ..
  55. Lee H, Yuan C, Hammet A, Mahajan A, Chen E, Wu M, et al. Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade. Mol Cell. 2008;30:767-78 pubmed publisher
    ..The Rad53-SCD1 has dual functions in regulating the activation of the Rad53-Dun1 checkpoint kinase cascade but with unknown ..
  56. Liang F, Wang Y. DNA damage checkpoints inhibit mitotic exit by two different mechanisms. Mol Cell Biol. 2007;27:5067-78 pubmed
    ..In response to DNA damage, two branches of the DNA damage checkpoint, Chk1 and Rad53, are activated in budding yeast to prevent anaphase entry and mitotic exit, allowing cells more time to repair ..
  57. 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
    In Saccharomyces cerevisiae, MEC1 and RAD53 are essential for cell growth and checkpoint function...
  58. Sidorova J, Breeden L. Rad53 checkpoint kinase phosphorylation site preference identified in the Swi6 protein of Saccharomyces cerevisiae. Mol Cell Biol. 2003;23:3405-16 pubmed
    b>Rad53 of Saccharomyces cerevisiae is a checkpoint kinase whose structure and function are conserved among eukaryotes...
  59. Zegerman P, Diffley J. Checkpoint-dependent inhibition of DNA replication initiation by Sld3 and Dbf4 phosphorylation. Nature. 2010;467:474-8 pubmed publisher
    ..Here we show that, analogous to the situation in the G1 phase, the Saccharomyces cerevisiae checkpoint kinase Rad53 inhibits both CDK- and DDK-dependent pathways, which acts redundantly to block further origin firing...
  60. Giannattasio M, Sommariva E, Vercillo R, Lippi Boncambi F, Liberi G, Foiani M, et al. A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1. Proc Natl Acad Sci U S A. 2002;99:12997-3002 pubmed
    ..step-by-step the signaling cascade, which is triggered by DNA lesions and requires the activity of Mec1 and Rad53 kinases...
  61. Donnianni R, Ferrari M, Lazzaro F, Clerici M, Tamilselvan Nachimuthu B, Plevani P, et al. Elevated levels of the polo kinase Cdc5 override the Mec1/ATR checkpoint in budding yeast by acting at different steps of the signaling pathway. PLoS Genet. 2010;6:e1000763 pubmed publisher
    ..of several Mec1/ATR targets, including Ddc2/ATRIP, the checkpoint mediator Rad9, and the transducer kinase Rad53/CHK2...
  62. Cartagena Lirola H, Guerini I, Manfrini N, Lucchini G, Longhese M. Role of the Saccharomyces cerevisiae Rad53 checkpoint kinase in signaling double-strand breaks during the meiotic cell cycle. Mol Cell Biol. 2008;28:4480-93 pubmed publisher
    ..DNA damage checkpoint response to accidental DSBs during mitosis requires the Rad53 effector kinase, whereas the meiosis-specific Mek1 kinase, together with Red1 and Hop1, mediates the recombination ..
  63. Kats E, Albuquerque C, Zhou H, Kolodner R. Checkpoint functions are required for normal S-phase progression in Saccharomyces cerevisiae RCAF- and CAF-I-defective mutants. Proc Natl Acad Sci U S A. 2006;103:3710-5 pubmed
    ..Our data suggest that RCAF defects lead to unstable replication forks that are then stabilized by replication checkpoint proteins, whereas CAF-I defects likely cause different types of DNA damage. ..
  64. Green E, Antczak A, Bailey A, Franco A, Wu K, Yates J, et al. Replication-independent histone deposition by the HIR complex and Asf1. Curr Biol. 2005;15:2044-9 pubmed
    ..These data indicate that the HIR complex and Asf1 proteins function together as a conserved eukaryotic pathway for histone replacement throughout the cell cycle. ..
  65. Hu F, Alcasabas A, Elledge S. Asf1 links Rad53 to control of chromatin assembly. Genes Dev. 2001;15:1061-6 pubmed
    Yeast defective in the checkpoint kinase Rad53 fail to recover from transient DNA replication blocks and synthesize intact chromosomes. The effectors of Rad53 relevant to this recovery process are unknown...
  66. Ogi H, Wang C, Nakai W, Kawasaki Y, Masumoto H. The role of the Saccharomyces cerevisiae Cdc7-Dbf4 complex in the replication checkpoint. Gene. 2008;414:32-40 pubmed publisher
    ..We found that in Cdc7-Dbf4-deficient cells exposed to replication stress, Rad53 remains in a hypophosphorylated form, anaphase spindle is elongated, and checkpoint-specific transcription is not ..
  67. Usui T, Ogawa H, Petrini J. A DNA damage response pathway controlled by Tel1 and the Mre11 complex. Mol Cell. 2001;7:1255-66 pubmed
    ..In mitotic cells, the Tel1-Mre11 complex pathway triggers Rad53 activation and its interaction with Rad9, whereas in meiosis it acts via Rad9 and the Rad53 paralog Mre4/Mek1...
  68. Koc A, Merrill G. Checkpoint deficient rad53-11 yeast cannot accumulate dNTPs in response to DNA damage. Biochem Biophys Res Commun. 2007;353:527-30 pubmed
    ..b>Rad53 is part of a protein kinase regulatory cascade that, conceptually, promotes dNTP accumulation in four ways: (1) it ..
  69. Pike B, Yongkiettrakul S, Tsai M, Heierhorst J. Mdt1, a novel Rad53 FHA1 domain-interacting protein, modulates DNA damage tolerance and G(2)/M cell cycle progression in Saccharomyces cerevisiae. Mol Cell Biol. 2004;24:2779-88 pubmed
    The Rad53 kinase plays a central role in yeast DNA damage checkpoints. Rad53 contains two FHA phosphothreonine-binding domains that are required for Rad53 activation and possibly downstream signaling...
  70. Gardner R, Putnam C, Weinert T. RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. EMBO J. 1999;18:3173-85 pubmed
    ..g. RAD9 and RAD24), those transducing a signal (MEC1, RAD53 and DUN1) or those participating more directly in arrest (PDS1)...
  71. Gibson D, Aparicio J, Hu F, Aparicio O. Diminished S-phase cyclin-dependent kinase function elicits vital Rad53-dependent checkpoint responses in Saccharomyces cerevisiae. Mol Cell Biol. 2004;24:10208-22 pubmed
    ..We present evidence for activation of Rad53 and Ddc2 functions with characteristics suggesting the presence of DNA damage...
  72. Game J, Kaufman P. Role of Saccharomyces cerevisiae chromatin assembly factor-I in repair of ultraviolet radiation damage in vivo. Genetics. 1999;151:485-97 pubmed
    ..We find an increased loss of telomeric gene silencing in rad6Delta cac1Delta and rad18Delta cac1Delta double mutants, suggesting that CAF-I and multiple factors in the postreplicative repair pathway influence chromosome structure. ..
  73. Huang M, Zhou Z, Elledge S. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell. 1998;94:595-605 pubmed
    ..Derepression of the Crt1 regulon suppresses the lethality of mec1 and rad53 null alleles and is essential for cell viability during replicative stress...
  74. Aucher W, Becker E, Ma E, Miron S, Martel A, Ochsenbein F, et al. A strategy for interaction site prediction between phospho-binding modules and their partners identified from proteomic data. Mol Cell Proteomics. 2010;9:2745-59 pubmed publisher
    ..The method was validated by a two-hybrid screen carried out using the ForkHead Associated (FHA)1 domain of Rad53, a key protein of Saccharomyces cerevisiae DNA checkpoint, as a bait...
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    ..The G1 delay undergone by spt16 mutants is not mediated by the DNA-damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197...
  76. Huang M, Elledge S. Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae. Mol Cell Biol. 1997;17:6105-13 pubmed
    ..RNR genes, RNR4 is inducible by DNA-damaging agents through the same signal transduction pathway involving MEC1, RAD53, and DUN1 kinase genes...