| Structural highlights
Function
[SHU2_YEAST] Plays a role in a RAD51/RAD54-dependent homologous recombination repair (HRR) pathway to repair MMS-induced lesions during S-phase. Required for error-free repair of spontaneous and induced DNA lesions to protect the genome from mutation.[1] [2] [3] [4] [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.[5] [6] [7] [8] [9] [10] [SHU1_YEAST] Plays a role in a RAD51/RAD54-dependent homologous recombination repair (HRR) pathway to repair MMS-induced lesions during S-phase.[11] [12] [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).[13] [14] [15] [16] [17]
Publication Abstract from PubMed
The Shu complex, a conserved regulator consisting of Csm2, Psy3, Shu1 and Shu2 in budding yeast, plays an important role in the assembly of the Rad51-ssDNA filament in homologous recombination. However, the molecular basis for the assembly of the Shu complex and its functional role in DNA repair is still elusive. Here, we report the crystal structure of the yeast Shu complex, revealing that Csm2, Psy3, Shu1 and Shu2 interact with each other in sequence to form a V-shape overall structure. Shu1 adopts a structure resembling the ATPase core domain of Rad51 and represents a new Rad51 paralog. Shu2 assumes a novel structural fold consisting of a conserved zinc-finger containing SWIM domain and a small insertion domain. The functional roles of the key residues are validated using mutagenesis and in vitro pull-down and in vivo yeast growth studies. Structural analysis together with available biological data identifies two potential DNA-binding sites, one of which might be responsible for binding the ssDNA region of the 3'-overhang DNA and the other for the dsDNA region. Collectively, these findings reveal the molecular basis for the assembly of the Shu complex and shed new insight on its functional role in homologous recombination.
Structural basis for the functional role of the Shu complex in homologous recombination.,Zhang S, Wang L, Tao Y, Bai T, Lu R, Zhang T, Chen J, Ding J Nucleic Acids Res. 2017 Oct 24. doi: 10.1093/nar/gkx992. PMID:29069504[18]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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:https://dx.doi.org/10.1073/pnas.2035018100
- ↑ 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
- ↑ Mankouri HW, Ngo HP, Hickson ID. Shu proteins promote the formation of homologous recombination intermediates that are processed by Sgs1-Rmi1-Top3. Mol Biol Cell. 2007 Oct;18(10):4062-73. Epub 2007 Aug 1. PMID:17671161 doi:https://dx.doi.org/10.1091/mbc.E07-05-0490
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1073/pnas.2035018100
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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:https://dx.doi.org/10.1073/pnas.2035018100
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Zhang S, Wang L, Tao Y, Bai T, Lu R, Zhang T, Chen J, Ding J. Structural basis for the functional role of the Shu complex in homologous recombination. Nucleic Acids Res. 2017 Oct 24. doi: 10.1093/nar/gkx992. PMID:29069504 doi:https://dx.doi.org/10.1093/nar/gkx992
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