Smc5/6 maintains stalled replication forks in a recombination-competent conformation

The Smc5/6 structural maintenance of chromosomes complex is required for efficient homologous recombination (HR). Defects in Smc5/6 result in chromosome mis‐segregation and fragmentation. By characterising two Schizosaccharomyces pombe smc6 mutants, we define two separate functions for Smc5/6 in HR....

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Vydáno v:	The EMBO journal Ročník 28; číslo 2; s. 144 - 155
Hlavní autoři:	Irmisch, Anja, Ampatzidou, Eleni, Mizuno, Ken'ichi, O'Connell, Matthew J, Murray, Johanne M
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Chichester, UK John Wiley & Sons, Ltd 21.01.2009 Nature Publishing Group UK Springer Nature B.V Nature Publishing Group
Témata:	Cell Cycle Proteins - genetics Cell Cycle Proteins - physiology Chromatin - genetics Chromatin - physiology Chromosomal Proteins, Non-Histone - genetics Chromosomal Proteins, Non-Histone - physiology Chromosomes Deoxyribonucleic acid DNA DNA Damage DNA Replication - genetics DNA Replication - physiology EMBO13 Genetic recombination Genomics Molecular biology Mutation Nucleic Acid Conformation Rad52 Rad52 DNA Repair and Recombination Protein - genetics Rad52 DNA Repair and Recombination Protein - metabolism recombination Recombination, Genetic replication fork stalling Schizosaccharomyces - genetics Schizosaccharomyces - physiology Schizosaccharomyces pombe Proteins - genetics Schizosaccharomyces pombe Proteins - physiology Smc5/6 replication fork stalling Rad52 recombination Smc5/6
ISSN:	0261-4189, 1460-2075, 1460-2075
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Shrnutí:	The Smc5/6 structural maintenance of chromosomes complex is required for efficient homologous recombination (HR). Defects in Smc5/6 result in chromosome mis‐segregation and fragmentation. By characterising two Schizosaccharomyces pombe smc6 mutants, we define two separate functions for Smc5/6 in HR. The first represents the previously described defect in processing recombination‐dependent DNA intermediates when replication forks collapse, which leads to increased rDNA recombination. The second novel function defines Smc5/6 as a positive regulator of recombination in the rDNA and correlates mechanistically with a requirement to load RPA and Rad52 onto chromatin genome‐wide when replication forks are stably stalled by nucleotide depletion. Rad52 is required for all HR repair, but Rad52 loading in response to replication fork stalling is unexpected and does not correlate with damage‐induced foci. We propose that Smc5/6 is required to maintain stalled forks in a stable recombination‐competent conformation primed for replication restart.
Bibliografie:	ArticleID:EMBJ2008273 Supplementary Information istex:C356B906D584FF7937D485BB435A1B475F005609 ark:/67375/WNG-TS7WF72V-5 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0261-4189 1460-2075 1460-2075
DOI:	10.1038/emboj.2008.273