Crystal Structure of Psy3-Csm2 complexCrystal Structure of Psy3-Csm2 complex

Structural highlights

3vu9 is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:PSY3, YLR376C, L8039.17 (Baker's yeast), CSM2, YIL132C (Baker's yeast)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PSY3_YEAST] Required for resistance to the DNA-damaging agents methyl methanesulfonate (MMS), cisplatin and oxaliplatin, but not to mitomycin C. Plays a role in protection against mutation accumulation. May be a component of the recombination-repair pathway.[1] [2] [3] [4] [5] [6] [CSM2_YEAST] Involved in chromosome segregation during meiosis. Promotes efficient recombinational repair and functions in the protection of the genome from spontaneous and induced DNA damage like mutations and gross chromosomal rearrangements (GCRs).[7] [8] [9] [10] [11]

Publication Abstract from PubMed

During homologous recombination, eukaryotic RecA homologue Rad51 assembles into a nucleoprotein filament on single-stranded DNA to catalyse homologous pairing and DNA-strand exchange with a homologous template. Rad51 nucleoprotein filaments are highly dynamic and regulated via the coordinated actions of various accessory proteins including Rad51 mediators. Here, we identify a new Rad51 mediator complex. The PCSS complex, comprising budding yeast Psy3, Csm2, Shu1 and Shu2 proteins, binds to recombination sites and is required for Rad51 assembly and function during meiosis. Within the hetero-tetramer, Psy3-Csm2 constitutes a core sub-complex with DNA-binding activity. In vitro, purified Psy3-Csm2 stabilizes the Rad51-single-stranded DNA complex independently of nucleotide cofactor. The mechanism of Rad51 stabilization is inferred by our high-resolution crystal structure, which reveals Psy3-Csm2 to be a structural mimic of the Rad51-dimer, a fundamental unit of the Rad51-filament. Together, these results reveal a novel molecular mechanism for this class of Rad51-mediators, which includes the human Rad51 paralogues.

A new protein complex promoting the assembly of Rad51 filaments.,Sasanuma H, Tawaramoto MS, Lao JP, Hosaka H, Sanda E, Suzuki M, Yamashita E, Hunter N, Shinohara M, Nakagawa A, Shinohara A Nat Commun. 2013;4:1676. doi: 10.1038/ncomms2678. PMID:23575680[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Hanway D, Chin JK, Xia G, Oshiro G, Winzeler EA, Romesberg FE. Previously uncharacterized genes in the UV- and MMS-induced DNA damage response in yeast. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10605-10. Epub 2002 Jul 29. PMID:12149442 doi:10.1073/pnas.152264899
  2. Chang M, Bellaoui M, Boone C, Brown GW. A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16934-9. Epub 2002 Dec 13. PMID:12482937 doi:10.1073/pnas.262669299
  3. Huang ME, Rio AG, Nicolas A, Kolodner RD. A genomewide screen in Saccharomyces cerevisiae for genes that suppress the accumulation of mutations. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11529-34. Epub 2003 Sep 12. PMID:12972632 doi:http://dx.doi.org/10.1073/pnas.2035018100
  4. Wu HI, Brown JA, Dorie MJ, Lazzeroni L, Brown JM. Genome-wide identification of genes conferring resistance to the anticancer agents cisplatin, oxaliplatin, and mitomycin C. Cancer Res. 2004 Jun 1;64(11):3940-8. PMID:15173006 doi:10.1158/0008-5472.CAN-03-3113
  5. Shor E, Weinstein J, Rothstein R. A genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: four genes involved in error-free DNA repair. Genetics. 2005 Mar;169(3):1275-89. Epub 2005 Jan 16. PMID:15654096 doi:10.1534/genetics.104.036764
  6. Ball LG, Zhang K, Cobb JA, Boone C, Xiao W. The yeast Shu complex couples error-free post-replication repair to homologous recombination. Mol Microbiol. 2009 Jul;73(1):89-102. Epub 2009 Jun 1. PMID:19496932 doi:MMI6748
  7. Rabitsch KP, Toth A, Galova M, Schleiffer A, Schaffner G, Aigner E, Rupp C, Penkner AM, Moreno-Borchart AC, Primig M, Esposito RE, Klein F, Knop M, Nasmyth K. A screen for genes required for meiosis and spore formation based on whole-genome expression. Curr Biol. 2001 Jul 10;11(13):1001-9. PMID:11470404
  8. Huang ME, Rio AG, Nicolas A, Kolodner RD. A genomewide screen in Saccharomyces cerevisiae for genes that suppress the accumulation of mutations. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11529-34. Epub 2003 Sep 12. PMID:12972632 doi:http://dx.doi.org/10.1073/pnas.2035018100
  9. Smith S, Hwang JY, Banerjee S, Majeed A, Gupta A, Myung K. Mutator genes for suppression of gross chromosomal rearrangements identified by a genome-wide screening in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9039-44. Epub 2004 Jun 7. PMID:15184655 doi:10.1073/pnas.0403093101
  10. Shor E, Weinstein J, Rothstein R. A genetic screen for top3 suppressors in Saccharomyces cerevisiae identifies SHU1, SHU2, PSY3 and CSM2: four genes involved in error-free DNA repair. Genetics. 2005 Mar;169(3):1275-89. Epub 2005 Jan 16. PMID:15654096 doi:10.1534/genetics.104.036764
  11. Ball LG, Zhang K, Cobb JA, Boone C, Xiao W. The yeast Shu complex couples error-free post-replication repair to homologous recombination. Mol Microbiol. 2009 Jul;73(1):89-102. Epub 2009 Jun 1. PMID:19496932 doi:MMI6748
  12. Sasanuma H, Tawaramoto MS, Lao JP, Hosaka H, Sanda E, Suzuki M, Yamashita E, Hunter N, Shinohara M, Nakagawa A, Shinohara A. A new protein complex promoting the assembly of Rad51 filaments. Nat Commun. 2013;4:1676. doi: 10.1038/ncomms2678. PMID:23575680 doi:10.1038/ncomms2678

3vu9, resolution 1.75Å

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