MEC1

Summary

Gene Symbol: MEC1
Description: protein kinase MEC1
Alias: ESR1, RAD31, SAD3, protein kinase MEC1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Morillo Huesca M, Maya D, Muñoz Centeno M, Singh R, Oreal V, Reddy G, et al. FACT prevents the accumulation of free histones evicted from transcribed chromatin and a subsequent cell cycle delay in G1. PLoS Genet. 2010;6:e1000964 pubmed publisher
  2. McCulley J, Petes T. Chromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms. Proc Natl Acad Sci U S A. 2010;107:11465-70 pubmed publisher
    ..The Saccharomyces cerevisiae homologs of ATM and ATR are Tel1p and Mec1p, respectively. Haploid tel1 mec1 strains have very short telomeres and very high rates of chromosomal aberrations...
  3. Ma Y, Greider C. Kinase-independent functions of TEL1 in telomere maintenance. Mol Cell Biol. 2009;29:5193-202 pubmed publisher
    ..These data indicate that Tel1p has two separate functions in telomere maintenance and that the Xrs2p-dependent recruitment of Tel1p to telomeres plays an important role even in the absence of its kinase activity. ..
  4. 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. ..
  5. Ho H, Burgess S. Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis. PLoS Genet. 2011;7:e1002351 pubmed publisher
    ..Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA...
  6. Wakayama T, Kondo T, Ando S, Matsumoto K, Sugimoto K. Pie1, a protein interacting with Mec1, controls cell growth and checkpoint responses in Saccharomyces cerevisiae. Mol Cell Biol. 2001;21:755-64 pubmed
    ..In budding yeast, the ATR family protein Mec1/Esr1 is essential for checkpoint responses and cell growth...
  7. 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. ..
  8. Clerici M, Baldo V, Mantiero D, Lottersberger F, Lucchini G, Longhese M. A Tel1/MRX-dependent checkpoint inhibits the metaphase-to-anaphase transition after UV irradiation in the absence of Mec1. Mol Cell Biol. 2004;24:10126-44 pubmed
    In Saccharomyces cerevisiae, Mec1/ATR plays a primary role in sensing and transducing checkpoint signals in response to different types of DNA lesions, while the role of the Tel1/ATM kinase in DNA damage checkpoints is not as well defined...
  9. 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
    ..At low concentrations of Rad53, preincubation of Rad53 with immune complexes containing the Mec1/Ddc2 complex can activate Rad53 kinase activity...

More Information

Publications93

  1. Merrill B, Holm C. A requirement for recombinational repair in Saccharomyces cerevisiae is caused by DNA replication defects of mec1 mutants. Genetics. 1999;153:595-605 pubmed
    ..We isolated 10 mec1 mutations that display synthetic lethality with rad52...
  2. Hirano Y, Sugimoto K. ATR homolog Mec1 controls association of DNA polymerase zeta-Rev1 complex with regions near a double-strand break. Curr Biol. 2006;16:586-90 pubmed
    ..In budding yeast, the ATR-homolog Mec1 plays a central role in the DNA-damage checkpoint response...
  3. Paciotti V, Clerici M, Scotti M, Lucchini G, Longhese M. Characterization of mec1 kinase-deficient mutants and of new hypomorphic mec1 alleles impairing subsets of the DNA damage response pathway. Mol Cell Biol. 2001;21:3913-25 pubmed
    ..The Saccharomyces cerevisiae Mec1 checkpoint protein, a phosphatidylinositol kinase-related protein, is required for transient cell cycle arrest in ..
  4. 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
    ..other RNR genes, RNR4 is inducible by DNA-damaging agents through the same signal transduction pathway involving MEC1, RAD53, and DUN1 kinase genes...
  5. 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 Rad53 is well understood and involves phosphorylation by the protein kinases Mec1 and Tel1 as well as in trans autophosphorylation by Rad53 itself...
  6. 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...
  7. Rodriguez J, Tsukiyama T. ATR-like kinase Mec1 facilitates both chromatin accessibility at DNA replication forks and replication fork progression during replication stress. Genes Dev. 2013;27:74-86 pubmed publisher
    ..We further found that Mec1, a key regulatory ATR-like kinase in the S-phase checkpoint, is required for both normal chromatin accessibility ..
  8. Kim E, Burke D. DNA damage activates the SAC in an ATM/ATR-dependent manner, independently of the kinetochore. PLoS Genet. 2008;4:e1000015 pubmed publisher
    ..b>Mec1 (ATR) and Tel1 (ATM) are also required, independently of Chk1 and Rad53, suggesting that Mec1 and Tel1 inhibit ..
  9. 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
    RAD53 and MEC1 are essential genes required for the transcriptional and cell cycle responses to DNA damage and DNA replication blocks...
  10. 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. ..
  11. Grandin N, Damon C, Charbonneau M. Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination. EMBO J. 2001;20:6127-39 pubmed
    ..We propose that Cdc13 prevents telomere uncapping and inhibits recombination between telomeric sequences through a pathway distinct from and complementary to that used by telomerase. ..
  12. 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
    Initiation of the DNA replication checkpoint in yeast is mainly mediated by Mec1 protein kinase, the ortholog of human ATR, while its homolog Tel1, the ortholog of human ATM, has a minor replication checkpoint function...
  13. Schlesinger M, Formosa T. POB3 is required for both transcription and replication in the yeast Saccharomyces cerevisiae. Genetics. 2000;155:1593-606 pubmed
    ..Mutation of the S phase checkpoint gene MEC1 caused pob3 mutants to lose viability rapidly under restrictive conditions, revealing defects in a process ..
  14. Lee S, Schwartz M, Duong J, Stern D. Rad53 phosphorylation site clusters are important for Rad53 regulation and signaling. Mol Cell Biol. 2003;23:6300-14 pubmed
    Budding yeast Rad53 is an essential protein kinase that is phosphorylated and activated in a MEC1- and TEL1-dependent manner in response to DNA damage...
  15. Puddu F, Piergiovanni G, Plevani P, Muzi Falconi M. Sensing of replication stress and Mec1 activation act through two independent pathways involving the 9-1-1 complex and DNA polymerase ?. PLoS Genet. 2011;7:e1002022 pubmed publisher
    ..The upstream kinase Mec1 is required to activate both signaling cascades together with the 9-1-1 PCNA-like complex and the Dpb11 (hTopBP1) ..
  16. Abdallah P, Luciano P, Runge K, Lisby M, Geli V, Gilson E, et al. A two-step model for senescence triggered by a single critically short telomere. Nat Cell Biol. 2009;11:988-93 pubmed publisher
  17. 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. ..
  18. Pike B, Heierhorst J. Mdt1 facilitates efficient repair of blocked DNA double-strand breaks and recombinational maintenance of telomeres. Mol Cell Biol. 2007;27:6532-45 pubmed
  19. Nakada D, Shimomura T, Matsumoto K, Sugimoto K. The ATM-related Tel1 protein of Saccharomyces cerevisiae controls a checkpoint response following phleomycin treatment. Nucleic Acids Res. 2003;31:1715-24 pubmed
    b>MEC1 and TEL1 encode ATR- and ATM-related proteins in the budding yeast Saccharomyces cerevisiae, respectively. Phleomycin is an agent that catalyzes double-strand breaks in DNA...
  20. 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 ..
  21. Tseng S, Lin J, Teng S. The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res. 2006;34:6327-36 pubmed
    ..Gel analysis showed that Cdc13p contains a Mec1/Tel1-dependent post-translational modification...
  22. Lee Y, Wang J, Stubbe J, Elledge S. Dif1 is a DNA-damage-regulated facilitator of nuclear import for ribonucleotide reductase. Mol Cell. 2008;32:70-80 pubmed publisher
    ..Dif1 is both cell-cycle and DNA-damage regulated, the latter of which occurs via the Mec1-Dun1 pathway...
  23. Mallory J, Bashkirov V, Trujillo K, Solinger J, Dominska M, Sung P, et al. Amino acid changes in Xrs2p, Dun1p, and Rfa2p that remove the preferred targets of the ATM family of protein kinases do not affect DNA repair or telomere length in Saccharomyces cerevisiae. DNA Repair (Amst). 2003;2:1041-64 pubmed
    ..As observed with Xrs2p, however, strains with mutations of DUN1 or RFA2 that eliminate SQ motifs have no effect on telomere length or DNA damage sensitivity. ..
  24. Baldo V, Testoni V, Lucchini G, Longhese M. Dominant TEL1-hy mutations compensate for Mec1 lack of functions in the DNA damage response. Mol Cell Biol. 2008;28:358-75 pubmed
    ..genome integrity is safeguarded by two highly conserved protein kinases that are called ATR and ATM for humans and Mec1 and Tel1 for Saccharomyces cerevisiae...
  25. 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
    RAD53 and MEC1 are essential Saccharomyces cerevisiae genes required for the DNA replication and DNA damage checkpoint responses. Their lethality can be suppressed by increasing the intracellular pool of deoxynucleotide triphosphates...
  26. 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
    ..to lesions such as double-strand breaks, is activated when the lesion promotes the association of the sensor kinase Mec1 and its targeting subunit Ddc2 with its activators Ddc1 (a member of the 9-1-1 complex) and Dpb11...
  27. 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 ..
  28. Gunjan A, Verreault A. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. Cell. 2003;115:537-49 pubmed
    Rad53 and Mec1 are protein kinases required for DNA replication and recovery from DNA damage in Saccharomyces cerevisiae...
  29. Myung K, Pennaneach V, Kats E, Kolodner R. Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability. Proc Natl Acad Sci U S A. 2003;100:6640-5 pubmed
    ..These results indicate that coupling of chromatin assembly to DNA replication and DNA repair is critical to maintaining genome stability. ..
  30. Maringele L, Lydall D. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes Dev. 2002;16:1919-33 pubmed
    ..We show that CHK1, MEC1, and RAD9 checkpoint genes are required for efficient cell cycle arrest of yku70Delta mutants cultured at 37 ..
  31. Chen S, Zhou H. Reconstitution of Rad53 activation by Mec1 through adaptor protein Mrc1. J Biol Chem. 2009;284:18593-604 pubmed publisher
    ..Using an activity-based assay for Rad53, we found that Mrc1, a replication fork-associated protein, cooperates with Mec1 to activate Rad53 directly...
  32. Grushcow J, Holzen T, Park K, Weinert T, Lichten M, Bishop D. Saccharomyces cerevisiae checkpoint genes MEC1, RAD17 and RAD24 are required for normal meiotic recombination partner choice. Genetics. 1999;153:607-20 pubmed
    ..Bypass of dmc1 arrest by mutation of the DNA damage checkpoint genes MEC1, RAD17, or RAD24 results in a dramatic loss of spore viability, suggesting that these genes play an important role ..
  33. Sun M, Fasullo M. Activation of the budding yeast securin Pds1 but not Rad53 correlates with double-strand break-associated G2/M cell cycle arrest in a mec1 hypomorphic mutant. Cell Cycle. 2007;6:1896-902 pubmed
    Budding yeast Mec1, encoded by the yeast ATR/ATM homolog, negatively regulates cell cycle progression by activating Rad53 (Chk2) and Chk1, two parallel downstream checkpoint pathways...
  34. Fukunaga K, Kwon Y, Sung P, Sugimoto K. Activation of protein kinase Tel1 through recognition of protein-bound DNA ends. Mol Cell Biol. 2011;31:1959-71 pubmed publisher
    ..The mre11-3 mutation abolishes DNA end-processing activity but does not affect the ability to enhance Tel1 activation. These results support a model in which MRX controls Tel1 activation by recognizing protein-bound DNA ends. ..
  35. Ye J, Ai X, Eugeni E, Zhang L, Carpenter L, Jelinek M, et al. Histone H4 lysine 91 acetylation a core domain modification associated with chromatin assembly. Mol Cell. 2005;18:123-30 pubmed
    ..These results indicate an important role for histone modifications outside the NH2-tail domains in the processes of chromatin assembly, DNA repair, and transcriptional silencing. ..
  36. 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
    ..This effect is conserved in budding yeast, as yeast cells lacking the related kinase Mec1 (ATM and Rad3-related (ATR in humans)) also fail to inhibit DNA synthesis in the presence of DNA damage...
  37. Rouse J. Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J. 2004;23:1188-97 pubmed
    ..These results identify Esc4p as an important new S-phase-specific target of Mec1p. ..
  38. 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. ..
  39. Fasullo M, Sun M. The Saccharomyces cerevisiae checkpoint genes RAD9, CHK1 and PDS1 are required for elevated homologous recombination in a mec1 (ATR) hypomorphic mutant. Cell Cycle. 2008;7:2418-26 pubmed
    ..The genetic requirements for hyper-recombination in ATR mutants are unknown. MEC1, the essential yeast ATR/ATM homolog, controls S and G(2) checkpoints and the DNA damage-inducibility of genes ..
  40. 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...
  41. Majka J, Burgers P. Clamping the Mec1/ATR checkpoint kinase into action. Cell Cycle. 2007;6:1157-60 pubmed
    The yeast checkpoint protein kinase Mec1, the ortholog of human ATR, is the essential upstream regulator of the cell cycle checkpoint in response to DNA damage and to stalling of DNA replication forks...
  42. Janke R, Herzberg K, Rolfsmeier M, Mar J, Bashkirov V, Haghnazari E, et al. A truncated DNA-damage-signaling response is activated after DSB formation in the G1 phase of Saccharomyces cerevisiae. Nucleic Acids Res. 2010;38:2302-13 pubmed publisher
    In Saccharomyces cerevisiae, the DNA damage response (DDR) is activated by the spatio-temporal colocalization of Mec1-Ddc2 kinase and the 9-1-1 clamp...
  43. 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
    Yeast Mec1/Ddc2 protein kinase, the ortholog of human ATR/ATRIP, plays a central role in the DNA damage checkpoint...
  44. 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...
  45. 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...
  46. Cremona C, Sarangi P, Yang Y, Hang L, Rahman S, Zhao X. Extensive DNA damage-induced sumoylation contributes to replication and repair and acts in addition to the mec1 checkpoint. Mol Cell. 2012;45:422-32 pubmed publisher
    ..We also show that DNA damage-induced sumoylation does not require Mec1 checkpoint signaling, and the presence of both enables optimal DNA damage resistance.
  47. 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. ..
  48. Yen J, Su N, Kaiser P. The yeast ubiquitin ligase SCFMet30 regulates heavy metal response. Mol Biol Cell. 2005;16:1872-82 pubmed
    ..Genetic analyses demonstrated a complex effect of cadmium on cell cycle regulation that might be important to safeguard cellular and genetic integrity when cells are exposed to heavy metals. ..
  49. Chan S, Chang J, Prescott J, Blackburn E. Altering telomere structure allows telomerase to act in yeast lacking ATM kinases. Curr Biol. 2001;11:1240-50 pubmed
    ..telomere structure in three different ways showed that telomerase can function in ATM kinase-deleted cells: tel1 mec1 cells senesced more slowly than tel1 mec1 cells that also lacked TLC1, which encodes telomerase RNA, suggesting ..
  50. 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
    ..Donor preference is independent of Mec1/ATR and Tel1/ATM checkpoint protein kinases but partially depends on casein kinase II...
  51. 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
    ..Relocation required the Nup84 complex and Mec1/Tel1 kinases...
  52. Makovets S, Blackburn E. DNA damage signalling prevents deleterious telomere addition at DNA breaks. Nat Cell Biol. 2009;11:1383-6 pubmed publisher
    ..Using yeast, we show that the main ATR/Mec1 DNA damage signalling pathway regulates telomerase action at DSBs...
  53. Cartagena Lirola H, Guerini I, Viscardi V, Lucchini G, Longhese M. Budding Yeast Sae2 is an In Vivo Target of the Mec1 and Tel1 Checkpoint Kinases During Meiosis. Cell Cycle. 2006;5:1549-59 pubmed
    ..Accordingly, Sae2 phosphorylation depends on the checkpoint kinases Mec1 and Tel1, whose simultaneous deletion also impairs meiotic DSB repair...
  54. Falk J, Chan A, Hoffmann E, Hochwagen A. A Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination. Dev Cell. 2010;19:599-611 pubmed publisher
    ..Zip1-S75 is a consensus site for the ATR-like checkpoint kinase Mec1, and centromere pairing is restored in mec1 mutants...
  55. Rouse J, Jackson S. Lcd1p recruits Mec1p to DNA lesions in vitro and in vivo. Mol Cell. 2002;9:857-69 pubmed
    ..Recruitment of Lcd1p to these lesions is independent of Mec1p and Rad9p/Rad24p. Thus, recruitment of Mec1p to DNA lesions by Lcd1p is crucial for the DNA damage response. ..
  56. Carballo J, Panizza S, Serrentino M, Johnson A, Geymonat M, Borde V, et al. Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery. PLoS Genet. 2013;9:e1003545 pubmed publisher
    ..conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through ..
  57. Carballo J, Cha R. Meiotic roles of Mec1, a budding yeast homolog of mammalian ATR/ATM. Chromosome Res. 2007;15:539-50 pubmed
    Budding yeast Mec1, a homolog of mammalian ATR/ATM, is an essential chromosome-based signal transduction protein. Mec1 is a key checkpoint regulator and plays a critical role in the maintenance of genome stability...
  58. Kitada T, Schleker T, Sperling A, Xie W, Gasser S, Grunstein M. ?H2A is a component of yeast heterochromatin required for telomere elongation. Cell Cycle. 2011;10:293-300 pubmed
    ..yeast telomeric and silent mating locus (HM) heterochromatin where ?H2A results from the action of kinases Tel1 and Mec1. Interestingly, mutation of ?H2A has no apparent effect on the binding of Sir (silent information regulator) ..
  59. Morrow D, Tagle D, Shiloh Y, Collins F, Hieter P. TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1. Cell. 1995;82:831-40 pubmed
    ..AT) have mutations in the AT mutated (ATM) gene, which is homologous to TEL1 and the checkpoint gene MEC1. A tel1 deletion mutant, unlike a mec1 deletion, is viable and does not exhibit increased sensitivity to DNA-..
  60. Downs J, Lowndes N, Jackson S. A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature. 2000;408:1001-4 pubmed
    ..breaks, and the phosphorylation of this motif in response to DNA damage is dependent on the PIKK family member Mec1. The motif is not necessary for Mec1-dependent cell-cycle or transcriptional responses to DNA damage, but is ..
  61. Cheng Y, Chuang C, Shen H, Lin F, Wang T. Three distinct modes of Mec1/ATR and Tel1/ATM activation illustrate differential checkpoint targeting during budding yeast early meiosis. Mol Cell Biol. 2013;33:3365-76 pubmed publisher
    ..Incomplete synapsis and unrepaired DNA are monitored by Mec1/Tel1-dependent checkpoint responses that prevent exit from the pachytene stage...
  62. Fasullo M, Sun M. UV but not X rays stimulate homologous recombination between sister chromatids and homologs in a Saccharomyces cerevisiae mec1 (ATR) hypomorphic mutant. Mutat Res. 2008;648:73-81 pubmed publisher
    b>MEC1, the essential yeast ATM/ATR homolog, prevents replication fork collapse and is required for the cellular response to DNA damage...
  63. Nakada D, Matsumoto K, Sugimoto K. ATM-related Tel1 associates with double-strand breaks through an Xrs2-dependent mechanism. Genes Dev. 2003;17:1957-62 pubmed
    ..Tel1 and the C terminus of Xrs2 are similarly involved in cell survival and Rad53 phosphorylation after DNA damage. Our findings suggest that the Tel1 association with DNA lesions is required for the activation of DNA damage responses. ..
  64. Hashash N, Johnson A, Cha R. Regulation of fragile sites expression in budding yeast by MEC1, RRM3 and hydroxyurea. J Cell Sci. 2011;124:181-5 pubmed publisher
    ..Here, we investigated this by examining the combined effects of rrm3?, mec1 and hydroxyurea (HU), three conditions that induce fragile sites, on expression of the replication slow zone (RSZ), ..
  65. D Amours D, Jackson S. The yeast Xrs2 complex functions in S phase checkpoint regulation. Genes Dev. 2001;15:2238-49 pubmed
    ..These results indicate that the Tel1p/ATM signaling pathway is conserved from yeast to humans and suggest that the Xrs2p/Nbs1 complexes act as signal modifiers. ..
  66. 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
    ..In budding yeast, ATM and ATR homologs are encoded by TEL1 and MEC1, respectively...
  67. Nakada D, Hirano Y, Tanaka Y, Sugimoto K. Role of the C terminus of Mec1 checkpoint kinase in its localization to sites of DNA damage. Mol Biol Cell. 2005;16:5227-35 pubmed
    ..In budding yeast, ATR homologue Mec1 plays a central role in DNA damage signaling...
  68. Lee Y, Elledge S. Control of ribonucleotide reductase localization through an anchoring mechanism involving Wtm1. Genes Dev. 2006;20:334-44 pubmed
    ..a homolog of WTM2, leads to the cytoplasmic localization of Rnr2/Rnr4, and increased hydroxyurea (HU)-resistance in mec1 mutants. Wtm1 binds Rnr2/4 complexes and release them to the cytoplasm in response to DNA damage...
  69. 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
    ..that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes...
  70. Ritchie K, Mallory J, Petes T. Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1999;19:6065-75 pubmed
    ..We show that a mutation in MEC1 (a gene related in sequence to TEL1 and ATM) reduces telomere length and that tel1 mec1 double mutant strains have ..
  71. 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 ..
  72. Hirano Y, Sugimoto K. Cdc13 telomere capping decreases Mec1 association but does not affect Tel1 association with DNA ends. Mol Biol Cell. 2007;18:2026-36 pubmed
    ..In budding yeast, Mec1 and Tel1 correspond to ATR and ATM, respectively...
  73. 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. ..
  74. 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. ..
  75. Gray S, Allison R, Garcia V, Goldman A, Neale M. Positive regulation of meiotic DNA double-strand break formation by activation of the DNA damage checkpoint kinase Mec1(ATR). Open Biol. 2013;3:130019 pubmed publisher
    ..Here, we use Saccharomyces cerevisiae to reveal that meiotic DSB formation is modulated by the Mec1(ATR) branch of the DNA damage signalling cascade, promoting DSB formation when Spo11-mediated catalysis is ..
  76. Anderson C, Blackburn E. Mec1 function in the DNA damage response does not require its interaction with Tel2. Cell Cycle. 2008;7:3695-8 pubmed
    ..that this mutation specifically disrupts the function of Tel1 and not the function of the closely related protein Mec1 (yeast ATR kinase) in DNA damage responses. Here we show that Tel2 and Mec1 interact in S...
  77. Toh G, Sugawara N, Dong J, Toth R, Lee S, Haber J, et al. Mec1/Tel1-dependent phosphorylation of Slx4 stimulates Rad1-Rad10-dependent cleavage of non-homologous DNA tails. DNA Repair (Amst). 2010;9:718-26 pubmed publisher
    ..We previously showed that Slx4 is dispensable for NER but is essential for SSA. Slx4 is phosphorylated by the Mec1 and Tel1 kinases after DNA damage on at least six Ser/Thr residues, and mutation of all six residues to Ala reduces ..
  78. Flott S, Rouse J. Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage. Biochem J. 2005;391:325-33 pubmed
    ..Slx4 phosphorylation is completely abolished in cells lacking the Mec1 and Tel1 protein kinases, critical regulators of genome stability, but is barely affected in the absence of both ..
  79. Searle J, Schollaert K, Wilkins B, Sanchez Y. The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression. Nat Cell Biol. 2004;6:138-45 pubmed
    ..is phosphorylated on PKA consensus sites after DNA damage, and this phosphorylation requires the Atr orthologue Mec1 and the PKA catalytic subunits Tpk1 and Tpk2...
  80. 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. ..
  81. Krishnan V, Nirantar S, Crasta K, Cheng A, Surana U. DNA replication checkpoint prevents precocious chromosome segregation by regulating spindle behavior. Mol Cell. 2004;16:687-700 pubmed
    ..b>Mec1 and Rad53 (human ATM/ATR- and Chk2-like kinases, respectively) are critical effectors of this pathway in yeast...
  82. 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...
  83. Pages V, Santa Maria S, Prakash L, Prakash S. Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast. Genes Dev. 2009;23:1438-49 pubmed publisher
    Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through ..
  84. Carballo J, Johnson A, Sedgwick S, Cha R. Phosphorylation of the axial element protein Hop1 by Mec1/Tel1 ensures meiotic interhomolog recombination. Cell. 2008;132:758-70 pubmed publisher
    ..Involvement of Mec1 and Tel1, the budding yeast homologs of the mammalian ATR and ATM kinases, in meiotic interhomlog bias has been ..