Article
- The EMBO Journal (2009) 28, 144 - 155
- doi:10.1038/emboj.2008.273
Subject Category:
Smc5/6 maintains stalled replication forks in a recombination-competent conformation
Anja Irmisch1, Eleni Ampatzidou1, Ken'ichi Mizuno1, Matthew J O'Connell2 & Johanne M Murray1
- Genome Damage and Stability Centre, University of Sussex, Brighton, UK
- Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA
Correspondence to:
Johanne M Murray, Genome Damage and Stability Centre, University of Sussex, School of Life Sciences, Falmer, Brighton, E. Sussex BN1 9RQ, UK. Tel.: +44 1273 877191; Fax: +44 1273 678121; E-mail: j.m.murray@sussex.ac.uk
Received 3 September 2008; Accepted 2 December 2008
Abstract
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.
Keywords:
- Rad52,
- recombination,
- replication fork stalling,
- Smc5/6
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