Swi2/Snf2-Related Translocases Prevent Accumulation of Toxic Rad51 Complexes during Mitotic Growth

• Published in: Molecular cell Vol. 39; no. 6; pp. 862 - 872
• Main Authors: Shah, Parisha P., Zheng, Xiuzhong, Epshtein, Anastasiya, Carey, Jeffrey N., Bishop, Douglas K., Klein, Hannah L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24-09-2010
• Subjects: Adenosine Triphosphatases - genetics; Cell Nucleus - metabolism; Cell Proliferation; Chromatin; Chromatin - metabolism; Chromosomal Instability - genetics; Diploidy; DNA Helicases - genetics; DNA Repair - genetics; DNA Repair Enzymes - genetics; DNA Topoisomerases - genetics; Gamma Rays; Gene Deletion; Gene Expression - genetics; Haploidy; Homeodomain Proteins - genetics; Mitosis - physiology; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; Replication Protein A - metabolism; Repressor Proteins - genetics; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae - radiation effects; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Transcription Factors; Transcription, Genetic - genetics; Transfection
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2010.08.028

Purified DNA translocases Rdh54 and Rad54 can dissociate complexes formed by eukaryotic RecA-like recombinases on double-stranded DNA. Here, we show that Rad51 complexes are dissociated by these translocases in mitotic cells. Rad51 overexpression blocked growth of cells deficient in Rdh54 activity. This toxicity was associated with accumulation of Rad51 foci on undamaged chromatin. At normal Rad51 levels, rdh54 deficiency resulted in slight elevation of Rad51 foci. A triple mutant lacking Rdh54, Rad54, and a third Swi2/Snf2 homolog Uls1 accumulated Rad51 foci, grew slowly, and suffered chromosome loss. Thus, Uls1 and Rad54 can partially substitute for Rdh54 in the removal of toxic, nondamage-associated Rad51-DNA complexes. Additional data suggest that the function of Rdh54 and Rad54 in removal of Rad51 foci is significantly specialized; Rad54 predominates for removal of damage-associated foci, and Rdh54 predominates for removal of nondamage-associated foci.
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► Unregulated Rad51 results in genomic instability ► Rdh54 translocase counteracts Rad51 accumulation on undamaged DNA ► Translocases Rad54 and Uls1 have a backup role in Rad51 removal from undamaged DNA ► Rad54 is more important than Rdh54 for removal of Rad51 from damaged DNA