rad32

Summary

Gene Symbol: rad32
Description: Rad32 nuclease
Alias: mre11, Rad32 nuclease
Species: fission yeast

Top Publications

  1. Schiller C, Lammens K, Guerini I, Coordes B, Feldmann H, Schlauderer F, et al. Structure of Mre11-Nbs1 complex yields insights into ataxia-telangiectasia-like disease mutations and DNA damage signaling. Nat Struct Mol Biol. 2012;19:693-700 pubmed publisher
    The Mre11-Rad50-Nbs1 (MRN) complex tethers, processes and signals DNA double-strand breaks, promoting genomic stability...
  2. Farah J, Cromie G, Smith G. Ctp1 and Exonuclease 1, alternative nucleases regulated by the MRN complex, are required for efficient meiotic recombination. Proc Natl Acad Sci U S A. 2009;106:9356-61 pubmed publisher
    ..We find that in the presence of the MRN (Rad32-Rad50-Nbs1) complex efficient recombination requires Ctp1, the ortholog of the nuclease Sae2, but not the nuclease ..
  3. Hartsuiker E, Mizuno K, Molnar M, Kohli J, Ohta K, Carr A. Ctp1CtIP and Rad32Mre11 nuclease activity are required for Rec12Spo11 removal, but Rec12Spo11 removal is dispensable for other MRN-dependent meiotic functions. Mol Cell Biol. 2009;29:1671-81 pubmed publisher
    ..This study demonstrates for the first time that Mre11 (Schizosaccharomyces pombe Rad32(Mre11)) nuclease activity is required for the removal of Rec12(Spo11)...
  4. Young J, Hyppa R, Smith G. Conserved and nonconserved proteins for meiotic DNA breakage and repair in yeasts. Genetics. 2004;167:593-605 pubmed
    ..Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts...
  5. Langerak P, Mejía Ramírez E, Limbo O, Russell P. Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks. PLoS Genet. 2011;7:e1002271 pubmed publisher
    The multifunctional Mre11-Rad50-Nbs1 (MRN) protein complex recruits ATM/Tel1 checkpoint kinase and CtIP/Ctp1 homologous recombination (HR) repair factor to double-strand breaks (DSBs)...
  6. Williams R, Moncalian G, Williams J, Yamada Y, Limbo O, Shin D, et al. Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair. Cell. 2008;135:97-109 pubmed publisher
    b>Mre11 forms the core of the multifunctional Mre11-Rad50-Nbs1 (MRN) complex that detects DNA double-strand breaks (DSBs), activates the ATM checkpoint kinase, and initiates homologous recombination (HR) repair of DSBs...
  7. Williams G, Williams R, Williams J, Moncalian G, Arvai A, Limbo O, et al. ABC ATPase signature helices in Rad50 link nucleotide state to Mre11 interface for DNA repair. Nat Struct Mol Biol. 2011;18:423-31 pubmed publisher
    The Rad50 ABC-ATPase complex with Mre11 nuclease is essential for dsDNA break repair, telomere maintenance and ataxia telangiectasia-mutated kinase checkpoint signaling...
  8. Limbo O, Chahwan C, Yamada Y, de Bruin R, Wittenberg C, Russell P. Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination. Mol Cell. 2007;28:134-46 pubmed
    The Mre11-Rad50-Nbs1 (MRN) complex is a primary sensor of DNA double-strand breaks (DSBs)...
  9. Williams R, Dodson G, Limbo O, Yamada Y, Williams J, Guenther G, et al. Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell. 2009;139:87-99 pubmed publisher
    The Nijmegen breakage syndrome 1 (Nbs1) subunit of the Mre11-Rad50-Nbs1 (MRN) complex protects genome integrity by coordinating double-strand break (DSB) repair and checkpoint signaling through undefined interactions with ATM, MDC1, and ..

More Information

Publications36

  1. Nakamura T, Moser B, Russell P. Telomere binding of checkpoint sensor and DNA repair proteins contributes to maintenance of functional fission yeast telomeres. Genetics. 2002;161:1437-52 pubmed
    ..Rad17, Rad26, Hus1, Crb2, Chk1, Cds1), Tel1, a telomere-binding protein (Taz1), and DNA repair proteins (Ku70, Rad32), we conclude that Rad3/Rad26 and Tel1/Rad32 represent two pathways required to maintain telomeres and prevent ..
  2. Porter Goff M, Rhind N. The role of MRN in the S-phase DNA damage checkpoint is independent of its Ctp1-dependent roles in double-strand break repair and checkpoint signaling. Mol Biol Cell. 2009;20:2096-107 pubmed publisher
    ..We find that several alleles of rad32 (the fission yeast homologue of mre11), along with ctp1Delta, are defective in double-strand break repair and most ..
  3. Hartsuiker E, Neale M, Carr A. Distinct requirements for the Rad32(Mre11) nuclease and Ctp1(CtIP) in the removal of covalently bound topoisomerase I and II from DNA. Mol Cell. 2009;33:117-23 pubmed publisher
    ..In this study, we provide evidence that the Schizosaccharomyces pombe Rad32(Mre11) nuclease activity is involved in the removal of both Top2 from 5' DNA ends as well as Top1 from 3' ends in ..
  4. Chahwan C, Nakamura T, Sivakumar S, Russell P, Rhind N. The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint. Mol Cell Biol. 2003;23:6564-73 pubmed
    ..Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA ..
  5. Rothenberg M, Kohli J, Ludin K. Ctp1 and the MRN-complex are required for endonucleolytic Rec12 removal with release of a single class of oligonucleotides in fission yeast. PLoS Genet. 2009;5:e1000722 pubmed publisher
    ..to the linear elements, Hop1 or Mek1, showed some Rec12 removal, a restoration depending on Ctp1 and Rad32 nuclease activity...
  6. Milman N, Higuchi E, Smith G. Meiotic DNA double-strand break repair requires two nucleases, MRN and Ctp1, to produce a single size class of Rec12 (Spo11)-oligonucleotide complexes. Mol Cell Biol. 2009;29:5998-6005 pubmed publisher
    ..On the basis of these and other data, we propose that Rad32 nuclease has the catalytic site for Rec12-oligonucleotide generation and is activated by Ctp1, which plays an ..
  7. You Z, Chahwan C, Bailis J, Hunter T, Russell P. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol. 2005;25:5363-79 pubmed
    ..ATM activation in response to DNA damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although the exact functional relationship between the MRN complex and ATM is uncertain...
  8. 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. ..
  9. Ueno M, Nakazaki T, Akamatsu Y, Watanabe K, Tomita K, Lindsay H, et al. Molecular characterization of the Schizosaccharomyces pombe nbs1+ gene involved in DNA repair and telomere maintenance. Mol Cell Biol. 2003;23:6553-63 pubmed
    ..Nbs1 physically interacts with the C-terminal half of Rad32, the Schizosaccharomyces pombe Mre11 homologue, in a yeast two-hybrid assay...
  10. Tomita K, Matsuura A, Caspari T, Carr A, Akamatsu Y, Iwasaki H, et al. Competition between the Rad50 complex and the Ku heterodimer reveals a role for Exo1 in processing double-strand breaks but not telomeres. Mol Cell Biol. 2003;23:5186-97 pubmed
    ..heterodimer inhibits processing of DSB ends and telomere ends by alternative nucleases in the absence of the Rad50-Rad32 protein complex...
  11. Limbo O, Moiani D, Kertokalio A, Wyman C, Tainer J, Russell P. Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-strand break repair. Nucleic Acids Res. 2012;40:11435-49 pubmed publisher
    The Mre11 complex (Mre11-Rad50-Nbs1 or MRN) binds double-strand breaks where it interacts with CtIP/Ctp1/Sae2 and ATM/Tel1 to preserve genome stability through its functions in homology-directed repair, checkpoint signaling and telomere ..
  12. Kuntz K, O Connell M. Initiation of DNA damage responses through XPG-related nucleases. EMBO J. 2013;32:290-302 pubmed publisher
    ..Thus, multiple nucleases collaborate to initiate DNA damage responses, highlighting the importance of these responses to cellular fitness. ..
  13. Ding L, Forsburg S. Essential domains of Schizosaccharomyces pombe Rad8 required for DNA damage response. G3 (Bethesda). 2014;4:1373-84 pubmed publisher
  14. Li Y, Wang J, Zhou G, Lajeunesse M, Le N, Stawicki B, et al. Nonhomologous End-Joining with Minimal Sequence Loss Is Promoted by the Mre11-Rad50-Nbs1-Ctp1 Complex in Schizosaccharomyces pombe. Genetics. 2017;206:481-496 pubmed publisher
    While the Mre11-Rad50-Nbs1 (MRN) complex has known roles in repair processes like homologous recombination and microhomology-mediated end-joining, its role in nonhomologous end-joining (NHEJ) is unclear as Saccharomyces cerevisiae,..
  15. Prudden J, Evans J, Hussey S, Deans B, O Neill P, Thacker J, et al. Pathway utilization in response to a site-specific DNA double-strand break in fission yeast. EMBO J. 2003;22:1419-30 pubmed
    ..We found that the homologous recombination (HR) genes rhp51(+), rad22A(+), rad32(+) and the nucleotide excision repair gene rad16(+) were required for efficient interchromosomal gene conversion...
  16. Wilson S, Warr N, Taylor D, Watts F. The role of Schizosaccharomyces pombe Rad32, the Mre11 homologue, and other DNA damage response proteins in non-homologous end joining and telomere length maintenance. Nucleic Acids Res. 1999;27:2655-61 pubmed
    The Schizosaccharomyces pombe homologue of Mre11, Rad32, is required for repair of UV- and ionising radiation-induced DNA damage and meiotic recombination...
  17. Paull T, Gellert M. The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Mol Cell. 1998;1:969-79 pubmed
    b>MRE11 and RAD50 are known to be required for nonhomologous joining of DNA ends in vivo...
  18. Willis N, Rhind N. The fission yeast Rad32(Mre11)-Rad50-Nbs1 complex acts both upstream and downstream of checkpoint signaling in the S-phase DNA damage checkpoint. Genetics. 2010;184:887-97 pubmed publisher
    The Mre11-Rad50-Nbs1 (MRN) heterotrimer plays various and complex roles in DNA damage repair and checkpoint signaling...
  19. Heideker J, Prudden J, Perry J, Tainer J, Boddy M. SUMO-targeted ubiquitin ligase, Rad60, and Nse2 SUMO ligase suppress spontaneous Top1-mediated DNA damage and genome instability. PLoS Genet. 2011;7:e1001320 pubmed publisher
    ..Collectively, these results reveal a unified role for STUbL, Rad60, and Nse2 in protecting genome stability against spontaneous Top1-mediated DNA damage. ..
  20. Ellermeier C, Smith G. Cohesins are required for meiotic DNA breakage and recombination in Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 2005;102:10952-7 pubmed
    ..Our results reveal a pathway, whose regulation is significantly different from that in the distantly related yeast Saccharomyces cerevisiae, for meiosis-specific chromosome differentiation and high-frequency recombination. ..
  21. Farah J, Cromie G, Steiner W, Smith G. A novel recombination pathway initiated by the Mre11/Rad50/Nbs1 complex eliminates palindromes during meiosis in Schizosaccharomyces pombe. Genetics. 2005;169:1261-74 pubmed
    DNA palindromes are rare in humans but are associated with meiosis-specific translocations. The conserved Mre11/Rad50/Nbs1 (MRN) complex is likely directly involved in processing palindromes through the homologous recombination pathway ..
  22. Caetano C, Limbo O, Farmer S, Klier S, Dovey C, Russell P, et al. Tolerance of deregulated G1/S transcription depends on critical G1/S regulon genes to prevent catastrophic genome instability. Cell Rep. 2014;9:2279-89 pubmed publisher
    ..Collectively, these results establish that, although deregulation of G1/S transcription is well tolerated by cells, nonessential G1/S target genes become crucial for preventing catastrophic genome instability. ..
  23. Tavassoli M, Shayeghi M, Nasim A, Watts F. Cloning and characterisation of the Schizosaccharomyces pombe rad32 gene: a gene required for repair of double strand breaks and recombination. Nucleic Acids Res. 1995;23:383-8 pubmed
    A new Schizosaccharomyces pombe mutant (rad32) which is sensitive to gamma and UV irradiation is described...
  24. Bonfils S, Rozalén A, Smith G, Moreno S, Martín Castellanos C. Functional interactions of Rec24, the fission yeast ortholog of mouse Mei4, with the meiotic recombination-initiation complex. J Cell Sci. 2011;124:1328-38 pubmed publisher
    ..Based on the recent report of Rec24 and Rec7 conservation, interaction between Rec24 and Rec7 might be widely conserved in DSB formation. ..
  25. Tomita K, Kibe T, Kang H, Seo Y, Uritani M, Ushimaru T, et al. Fission yeast Dna2 is required for generation of the telomeric single-strand overhang. Mol Cell Biol. 2004;24:9557-67 pubmed
    It has been suggested that the Schizosaccharomyces pombe Rad50 (Rad50-Rad32-Nbs1) complex is required for the resection of the C-rich strand at telomere ends in taz1-d cells...
  26. Reis C, Batista S, Ferreira M. The fission yeast MRN complex tethers dysfunctional telomeres for NHEJ repair. EMBO J. 2012;31:4576-86 pubmed publisher
    ..Neither Tel1(ATM) activation nor 5'-end resection was required for telomere fusion. Nuclease activity of Rad32(MRE11) was also dispensable for NHEJ...
  27. Almeida H, Godinho Ferreira M. Spontaneous telomere to telomere fusions occur in unperturbed fission yeast cells. Nucleic Acids Res. 2013;41:3056-67 pubmed publisher
    ..Thus, telomeres undergo fusions prior to becoming critically short, possibly through transient deprotection. These dysfunction events induce chromosome instability and may underlie early tumourigenesis. ..