Gene Symbol: mrc1
Description: protein mrc1
Alias: protein mrc1
Species: fission yeast
Products:     mrc1

Top Publications

  1. Tanaka T, Yokoyama M, Matsumoto S, Fukatsu R, You Z, Masai H. Fission yeast Swi1-Swi3 complex facilitates DNA binding of Mrc1. J Biol Chem. 2010;285:39609-22 pubmed publisher
    Replication fork protection complex Swi1-Swi3 and replication checkpoint mediator Mrc1 are required for maintenance of replication fork integrity during the course of DNA replication in the fission yeast Schizosaccharomyces pombe...
  2. Alcasabas A, Osborn A, Bachant J, Hu F, Werler P, Bousset K, et al. Mrc1 transduces signals of DNA replication stress to activate Rad53. Nat Cell Biol. 2001;3:958-65 pubmed
    ..We describe a conserved protein Mrc1, mediator of the replication checkpoint, required for activation of ScRad53 and SpCds1 during replication ..
  3. Matsumoto S, Ogino K, Noguchi E, Russell P, Masai H. Hsk1-Dfp1/Him1, the Cdc7-Dbf4 kinase in Schizosaccharomyces pombe, associates with Swi1, a component of the replication fork protection complex. J Biol Chem. 2005;280:42536-42 pubmed
    ..These data suggest that Hsk1-Dfp1/Him1 and Swi1-Swi3 complexes have interrelated roles in stabilization of arrested replication forks. ..
  4. Zhao H, Russell P. DNA binding domain in the replication checkpoint protein Mrc1 of Schizosaccharomyces pombe. J Biol Chem. 2004;279:53023-7 pubmed
    ..In the fission yeast Schizosaccharomyces pombe, Mrc1 is a replication checkpoint adaptor protein that allows the sensor kinase Rad3-Rad26 to activate the effector ..
  5. Xu Y, Davenport M, Kelly T. Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1 in fission yeast. Genes Dev. 2006;20:990-1003 pubmed
    ..Activation of Cds1 is known to require the upstream kinase Rad3 and the mediator Mrc1, but the biochemical mechanism of activation is not well understood...
  6. Nitani N, Nakamura K, Nakagawa C, Masukata H, Nakagawa T. Regulation of DNA replication machinery by Mrc1 in fission yeast. Genetics. 2006;174:155-65 pubmed
    ..b>Mrc1 is required to activate Cds1 and prevent the replication machinery from uncoupling from DNA synthesis...
  7. Shimmoto M, Matsumoto S, Odagiri Y, Noguchi E, Russell P, Masai H. Interactions between Swi1-Swi3, Mrc1 and S phase kinase, Hsk1 may regulate cellular responses to stalled replication forks in fission yeast. Genes Cells. 2009;14:669-82 pubmed publisher
    The Swi1-Swi3 replication fork protection complex and Mrc1 protein are required for stabilization of stalled replication forks in fission yeast. Hsk1 kinase also plays roles in checkpoint responses elicited by arrested replication forks...
  8. Yin L, Locovei A, D URSO G. Activation of the DNA damage checkpoint in mutants defective in DNA replication initiation. Mol Biol Cell. 2008;19:4374-82 pubmed publisher
    ..Chk1 is active in rid mutants, and rid mutant viability is dependent on the DNA damage checkpoint, and surprisingly Mrc1, a protein required for activation of Cds1...
  9. Zhao H, Tanaka K, Nogochi E, Nogochi C, Russell P. Replication checkpoint protein Mrc1 is regulated by Rad3 and Tel1 in fission yeast. Mol Cell Biol. 2003;23:8395-403 pubmed
    Fission yeast Mrc1 (mediator of replication checkpoint 1) is an adaptor checkpoint protein required for Rad3-dependent activation of the checkpoint kinase Cds1 in response to arrest of replication forks...

More Information


  1. Tanaka K, Russell P. Mrc1 channels the DNA replication arrest signal to checkpoint kinase Cds1. Nat Cell Biol. 2001;3:966-72 pubmed
    ..Here we describe a novel checkpoint gene in fission yeast, mrc1 (mediator of replication checkpoint), that confers activation of the checkpoint kinase Cds1 to DNA synthesis (S) ..
  2. Shikata M, Ishikawa F, Kanoh J. Tel2 is required for activation of the Mrc1-mediated replication checkpoint. J Biol Chem. 2007;282:5346-55 pubmed
    ..we report that in the fission yeast, Schizosaccharomyces pombe, Tel2 is required for efficient phosphorylation of Mrc1, a mediator of DNA replication checkpoint signaling, and for activation of Cds1, a replication checkpoint kinase, ..
  3. Willis N, Rhind N. Mus81, Rhp51(Rad51), and Rqh1 form an epistatic pathway required for the S-phase DNA damage checkpoint. Mol Biol Cell. 2009;20:819-33 pubmed publisher
    ..We propose that restraining recombination is required for the slowing of replication in response to DNA damage. ..
  4. Hayano M, Kanoh Y, Matsumoto S, Masai H. Mrc1 marks early-firing origins and coordinates timing and efficiency of initiation in fission yeast. Mol Cell Biol. 2011;31:2380-91 pubmed publisher
    How early- and late-firing origins are selected on eukaryotic chromosomes is largely unknown. Here, we show that Mrc1, a conserved factor required for stabilization of stalled replication forks, selectively binds to the early-firing ..
  5. Matsumoto S, Shimmoto M, Kakusho N, Yokoyama M, Kanoh Y, Hayano M, et al. Hsk1 kinase and Cdc45 regulate replication stress-induced checkpoint responses in fission yeast. Cell Cycle. 2010;9:4627-37 pubmed
    ..fork arrest activates the replication checkpoint effector kinase Cds1(Chk2/Rad53) through the Rad3(ATR/Mec1)-Mrc1(Claspin) pathway...
  6. Tanaka K, Russell P. Cds1 phosphorylation by Rad3-Rad26 kinase is mediated by forkhead-associated domain interaction with Mrc1. J Biol Chem. 2004;279:32079-86 pubmed
    ..b>Mrc1 (mediator of the replication checkpoint-1) and Rad3-Rad26 kinase are required for Cds1 activation, but exactly how ..
  7. Dolan W, Le A, Schmidt H, Yuan J, Green M, Forsburg S. Fission yeast Hsk1 (Cdc7) kinase is required after replication initiation for induced mutagenesis and proper response to DNA alkylation damage. Genetics. 2010;185:39-53 pubmed publisher
    ..We conclude that Hsk1-Dfp1 kinase functions post-initiation to maintain replication fork stability, an activity potentially mediated by the C terminus of Dfp1. ..
  8. Ranatunga N, Forsburg S. Characterization of a Novel MMS-Sensitive Allele of Schizosaccharomyces pombe mcm4. G3 (Bethesda). 2016;6:3049-3063 pubmed publisher
    ..Surprisingly, we found that the deletion of rif1+ suppressed the MMS-sensitive phenotype without affecting temperature sensitivity. Together, these data suggest that mcm4-c106 destabilizes replisome structure. ..
  9. Matsumoto S, Kanoh Y, Shimmoto M, Hayano M, Ueda K, Fukatsu R, et al. Checkpoint-Independent Regulation of Origin Firing by Mrc1 through Interaction with Hsk1 Kinase. Mol Cell Biol. 2017;37: pubmed publisher
    b>Mrc1 is a conserved checkpoint mediator protein that transduces the replication stress signal to the downstream effector kinase...
  10. Li P, Petreaca R, Jensen A, Yuan J, Green M, Forsburg S. Replication fork stability is essential for the maintenance of centromere integrity in the absence of heterochromatin. Cell Rep. 2013;3:638-45 pubmed publisher
    ..Thus, heterochromatin proteins and replication fork protection mechanisms work in concert to prevent abnormal recombination, preserve centromere integrity, and ensure faithful chromosome segregation...
  11. Nakamura T, Du L, Redon C, Russell P. Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast. Mol Cell Biol. 2004;24:6215-30 pubmed
    ..This function correlates with evidence that gamma-H2AX regulates recruitment of several BRCA1 carboxyl terminus domain-containing proteins (NBS1, 53BP1, MDC1/NFBD1, and BRCA1) in mammals. ..
  12. Matsumoto S, Hayano M, Kanoh Y, Masai H. Multiple pathways can bypass the essential role of fission yeast Hsk1 kinase in DNA replication initiation. J Cell Biol. 2011;195:387-401 pubmed publisher
    ..Here, we show that viability of fission yeast hsk1? cells can be restored by loss of mrc1, which is required for maintenance of replication fork integrity, by cds1?, or by a checkpoint-deficient mutant of ..
  13. Schonbrun M, Kolesnikov M, Kupiec M, Weisman R. TORC2 is required to maintain genome stability during S phase in fission yeast. J Biol Chem. 2013;288:19649-60 pubmed publisher
    ..Our findings indicate that TORC2 is required for genome integrity. This may be relevant for the growing amount of evidence implicating TORC2 in cancer development...
  14. Dutta C, Rhind N. The role of specific checkpoint-induced S-phase transcripts in resistance to replicative stress. PLoS ONE. 2009;4:e6944 pubmed publisher
    ..Finally, we investigate the roles of two specific transcripts: mik1 and mrc1. These results demonstrate the general importance of checkpoint regulation of G1/S transcription in response to ..
  15. Zech J, Godfrey E, Masai H, Hartsuiker E, Dalgaard J. The DNA-Binding Domain of S. pombe Mrc1 (Claspin) Acts to Enhance Stalling at Replication Barriers. PLoS ONE. 2015;10:e0132595 pubmed publisher
    ..Using a new genetic screen we identified Mrc1 (S. cerevisiae Mrc1/metazoan Claspin) as a replisome component involved in replication stalling...
  16. Sanders S, Portoso M, Mata J, Bahler J, Allshire R, Kouzarides T. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell. 2004;119:603-14 pubmed
    ..These results argue that H4-K20 methylation functions as a "histone mark" required for the recruitment of the checkpoint protein Crb2. ..
  17. Schonbrun M, Laor D, López Maury L, Bahler J, Kupiec M, Weisman R. TOR complex 2 controls gene silencing, telomere length maintenance, and survival under DNA-damaging conditions. Mol Cell Biol. 2009;29:4584-94 pubmed publisher
    ..These data place TOR proteins in line with other PIKK members, such as ATM and ATR, as guardians of genome stability. ..
  18. Hayano M, Kanoh Y, Matsumoto S, Renard Guillet C, Shirahige K, Masai H. Rif1 is a global regulator of timing of replication origin firing in fission yeast. Genes Dev. 2012;26:137-50 pubmed publisher
    ..Our data demonstrate that Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes. ..
  19. Xu Y. Inner nuclear membrane protein Lem2 facilitates Rad3-mediated checkpoint signaling under replication stress induced by nucleotide depletion in fission yeast. Cell Signal. 2016;28:235-45 pubmed publisher
    ..perturbed replication forks activate the sensor kinase Rad3 (ATR/Mec1), which works cooperatively with mediator Mrc1 and the 9-1-1 checkpoint clamp to phosphorylate the effector kinase Cds1 (CHK2/Rad53)...
  20. Garabedian M, Noguchi C, Ziegler M, Das M, Singh T, Harper L, et al. The double-bromodomain proteins Bdf1 and Bdf2 modulate chromatin structure to regulate S-phase stress response in Schizosaccharomyces pombe. Genetics. 2012;190:487-500 pubmed publisher
    ..deletion of bdf1 or bdf2 partially suppressed sensitivity of various checkpoint mutants including swi1?, mrc1?, cds1?, crb2?, chk1?, and rad3?, to hydroxyurea, a compound that stalls replication forks and activates the Cds1-..
  21. S nchez A, Sharma S, Rozenzhak S, Roguev A, Krogan N, Chabes A, et al. Replication fork collapse and genome instability in a deoxycytidylate deaminase mutant. Mol Cell Biol. 2012;32:4445-54 pubmed publisher
    ..Moreover, Brc1 suppresses spontaneous mutagenesis in dcd1? cells. We propose that replication forks stall and collapse in dcd1? cells, burdening DNA damage and checkpoint responses to maintain genome integrity...
  22. Haldar D, Kamakaka R. Schizosaccharomyces pombe Hst4 functions in DNA damage response by regulating histone H3 K56 acetylation. Eukaryot Cell. 2008;7:800-13 pubmed publisher
    ..We propose that Hst4 is a deacetylase involved in the restoration of chromatin structure following the S phase of cell cycle and DNA damage response. ..
  23. Ding L, Forsburg S. Essential domains of Schizosaccharomyces pombe Rad8 required for DNA damage response. G3 (Bethesda). 2014;4:1373-84 pubmed publisher
  24. Locovei A, Yin L, D URSO G. A genetic screen for replication initiation defective (rid) mutants in Schizosaccharomyces pombe. Cell Div. 2010;5:20 pubmed publisher