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Gene Review

MEC1  -  Mec1p

Saccharomyces cerevisiae S288c

Synonyms: ATR homolog, DNA-damage checkpoint kinase MEC1, ESR1, Mitosis entry checkpoint protein 1, RAD31, ...
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Disease relevance of MEC1


High impact information on MEC1

  • Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast [5].
  • In contrast, inactivation of Mec1 resulted in more inversion translocations such as the isochromosomes seen in human tumors [5].
  • 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 [6].
  • MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks [7].
  • Derepression of the Crt1 regulon suppresses the lethality of mec1 and rad53 null alleles and is essential for cell viability during replicative stress [8].

Biological context of MEC1


Anatomical context of MEC1


Associations of MEC1 with chemical compounds

  • 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 [14].
  • We propose that the essential function for MEC1 may be the same as its checkpoint function during hydroxyurea treatment, namely, to slow S phase when nucleotides are limiting [15].
  • MMS induction of UMP1 expression occurs at the transcriptional level and is independent of the activity of the regulatory checkpoint kinases encoded by MEC1 [16].
  • Other aspects of the genomic responses were independent of Mec1p, and likely independent of DNA damage, suggesting the pleiotropic effects of MMS and ionizing radiation [17].
  • Here we show that the DNA-alkylating agent methyl methanesulphonate (MMS) profoundly reduces the rate of DNA replication fork progression; however, this moderation does not require Rad53 or Mec1 [18].

Physical interactions of MEC1

  • Finally, we reveal that endogenous Mec1p co-immunoprecipitates with Lcd1p both before and after treatment with DNA-damaging agents [13].
  • We sought to determine whether the mediator requirement could be circumvented by making fusion proteins between the Mec1 binding partner Ddc2p and Rad53p [19].
  • In G(1) cells expressing the mutation, the signaling cannot proceed any further along the pathway, indicating that the Rad17 complex acts after the activation of Mec1, possibly recruiting targets for the kinase [20].
  • Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway [21].

Enzymatic interactions of MEC1


Regulatory relationships of MEC1

  • Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways [26].
  • These results indicate that Rph1 phosphorylation is under the control of the Mec1-Rad53 damage checkpoint pathway [27].
  • These data suggest, first, that the checkpoint sliding clamp regulates and/or recruits some nucleases for degradation, and, second, that Mec1 activates Rad9 to activate Rad53 to inhibit degradation [28].
  • Finally, analysis of double mutants suggests a minor role for Mec1 in promoting Rad24-dependent degradation of dsDNA [28].
  • We found that UV irradiation in G(1) in the absence of Mec1 activates a Tel1/MRX-dependent checkpoint, which specifically inhibits the metaphase-to-anaphase transition [29].

Other interactions of MEC1

  • Second, mec1 and rad24 single mutants (DMC1+) appear to undergo MI before all recombination events are complete [30].
  • Analysis of viable null alleles revealed that Mec1 plays a greater role in response to inhibition of DNA synthesis than Rad53 [9].
  • We report here that multiple Mec1/Tel1 consensus [S/T]Q sites within Rad9 are phosphorylated in response to DNA damage [31].
  • 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 [11].
  • We suggest that Rad9p and Ddc1p might function in separated branches of the DNA damage checkpoint pathway, playing different roles in determining Mec1p activity and/or substrate specificity [32].

Analytical, diagnostic and therapeutic context of MEC1


  1. Involvement of the PP2C-like phosphatase Ptc2p in the DNA checkpoint pathways of Saccharomyces cerevisiae. Marsolier, M.C., Roussel, P., Leroy, C., Mann, C. Genetics (2000) [Pubmed]
  2. TEL1, an S. cerevisiae homolog of the human gene mutated in ataxia telangiectasia, is functionally related to the yeast checkpoint gene MEC1. Morrow, D.M., Tagle, D.A., Shiloh, Y., Collins, F.S., Hieter, P. Cell (1995) [Pubmed]
  3. Rfc5, a replication factor C component, is required for regulation of Rad53 protein kinase in the yeast checkpoint pathway. Sugimoto, K., Ando, S., Shimomura, T., Matsumoto, K. Mol. Cell. Biol. (1997) [Pubmed]
  4. The Saccharomyces cerevisiae MEC1 gene, which encodes a homolog of the human ATM gene product, is required for G1 arrest following radiation treatment. Siede, W., Allen, J.B., Elledge, S.J., Friedberg, E.C. J. Bacteriol. (1996) [Pubmed]
  5. Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast. Pennaneach, V., Kolodner, R.D. Nat. Genet. (2004) [Pubmed]
  6. A Rad53 kinase-dependent surveillance mechanism that regulates histone protein levels in S. cerevisiae. Gunjan, A., Verreault, A. Cell (2003) [Pubmed]
  7. MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks. Mills, K.D., Sinclair, D.A., Guarente, L. Cell (1999) [Pubmed]
  8. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Huang, M., Zhou, Z., Elledge, S.J. Cell (1998) [Pubmed]
  9. Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Desany, B.A., Alcasabas, A.A., Bachant, J.B., Elledge, S.J. Genes Dev. (1998) [Pubmed]
  10. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Weinert, T.A., Kiser, G.L., Hartwell, L.H. Genes Dev. (1994) [Pubmed]
  11. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Zhao, X., Muller, E.G., Rothstein, R. Mol. Cell (1998) [Pubmed]
  12. The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage. Zhao, X., Chabes, A., Domkin, V., Thelander, L., Rothstein, R. EMBO J. (2001) [Pubmed]
  13. LCD1: an essential gene involved in checkpoint control and regulation of the MEC1 signalling pathway in Saccharomyces cerevisiae. Rouse, J., Jackson, S.P. EMBO J. (2000) [Pubmed]
  14. Rad53-dependent phosphorylation of Swi6 and down-regulation of CLN1 and CLN2 transcription occur in response to DNA damage in Saccharomyces cerevisiae. Sidorova, J.M., Breeden, L.L. Genes Dev. (1997) [Pubmed]
  15. Interaction between the MEC1-dependent DNA synthesis checkpoint and G1 cyclin function in Saccharomyces cerevisiae. Vallen, E.A., Cross, F.R. Genetics (1999) [Pubmed]
  16. Expression of UMP1 is inducible by DNA damage and required for resistance of S. cerevisiae cells to UV light. Mieczkowski, P., Dajewski, W., Podlaska, A., Skoneczna, A., Ciesla, Z., Sledziewska-Gójska, E. Curr. Genet. (2000) [Pubmed]
  17. Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. Gasch, A.P., Huang, M., Metzner, S., Botstein, D., Elledge, S.J., Brown, P.O. Mol. Biol. Cell (2001) [Pubmed]
  18. Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint. Tercero, J.A., Diffley, J.F. Nature (2001) [Pubmed]
  19. A Ddc2-Rad53 fusion protein can bypass the requirements for RAD9 and MRC1 in Rad53 activation. Lee, S.J., Duong, J.K., Stern, D.F. Mol. Biol. Cell (2004) [Pubmed]
  20. A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1. Giannattasio, M., Sommariva, E., Vercillo, R., Lippi-Boncambi, F., Liberi, G., Foiani, M., Plevani, P., Muzi-Falconi, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. Requirement of the Mre11 complex and exonuclease 1 for activation of the Mec1 signaling pathway. Nakada, D., Hirano, Y., Sugimoto, K. Mol. Cell. Biol. (2004) [Pubmed]
  22. Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism. Naiki, T., Wakayama, T., Nakada, D., Matsumoto, K., Sugimoto, K. Mol. Cell. Biol. (2004) [Pubmed]
  23. 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. Mallory, J.C., Bashkirov, V.I., Trujillo, K.M., Solinger, J.A., Dominska, M., Sung, P., Heyer, W.D., Petes, T.D. DNA Repair (Amst.) (2003) [Pubmed]
  24. Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. Rouse, J. EMBO J. (2004) [Pubmed]
  25. Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage. Flott, S., Rouse, J. Biochem. J. (2005) [Pubmed]
  26. Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways. Sun, Z., Fay, D.S., Marini, F., Foiani, M., Stern, D.F. Genes Dev. (1996) [Pubmed]
  27. Phosphorylation of Rph1, a damage-responsive repressor of PHR1 in Saccharomyces cerevisiae, is dependent upon Rad53 kinase. Kim, E.M., Jang, Y.K., Park, S.D. Nucleic Acids Res. (2002) [Pubmed]
  28. Mec1 and Rad53 inhibit formation of single-stranded DNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Jia, X., Weinert, T., Lydall, D. Genetics (2004) [Pubmed]
  29. A Tel1/MRX-dependent checkpoint inhibits the metaphase-to-anaphase transition after UV irradiation in the absence of Mec1. Clerici, M., Baldo, V., Mantiero, D., Lottersberger, F., Lucchini, G., Longhese, M.P. Mol. Cell. Biol. (2004) [Pubmed]
  30. A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Lydall, D., Nikolsky, Y., Bishop, D.K., Weinert, T. Nature (1996) [Pubmed]
  31. Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA damage checkpoint. Schwartz, M.F., Duong, J.K., Sun, Z., Morrow, J.S., Pradhan, D., Stern, D.F. Mol. Cell (2002) [Pubmed]
  32. Mec1p is essential for phosphorylation of the yeast DNA damage checkpoint protein Ddc1p, which physically interacts with Mec3p. Paciotti, V., Lucchini, G., Plevani, P., Longhese, M.P. EMBO J. (1998) [Pubmed]
  33. Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae. Mieczkowski, P.A., Mieczkowska, J.O., Dominska, M., Petes, T.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  34. S. cerevisiae Tel1p and Mre11p are required for normal levels of Est1p and Est2p telomere association. Goudsouzian, L.K., Tuzon, C.T., Zakian, V.A. Mol. Cell (2006) [Pubmed]
  35. Evidence of meiotic crossover control in Saccharomyces cerevisiae through Mec1-mediated phosphorylation of replication protein A. Bartrand, A.J., Iyasu, D., Marinco, S.M., Brush, G.S. Genetics (2006) [Pubmed]
  36. Artificial antisense RNA regulation of YBR1012 (YBR136w), an essential gene from Saccharomyces cerevisiae which is important for progression through G1/S. Nasr, F., Bécam, A.M., Brown, S.C., De Nay, D., Slonimski, P.P., Herbert, C.J. Mol. Gen. Genet. (1995) [Pubmed]
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