The homologous recombination machinery modulates the formation of RNA–DNA hybrids and associated chromosome instability

eLife

Steven K Gore¹  Douglas Koshland²  Lamia Wahba² 

[1] Department of Biology, Johns Hopkins University, Baltimore, United States;Department of Cell and Molecular Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States;

关键词: R loop;    RNA-DNA hybrid;    Rad51;    genome instability;    DNA repair;   

DOI  :  10.7554/eLife.00505

来源: DOAJ

【 摘 要 】

Genome instability in yeast and mammals is caused by RNA–DNA hybrids that form as a result of defects in different aspects of RNA biogenesis. We report that in yeast mutants defective for transcription repression and RNA degradation, hybrid formation requires Rad51p and Rad52p. These proteins normally promote DNA–DNA strand exchange in homologous recombination. We suggest they also directly promote the DNA–RNA strand exchange necessary for hybrid formation since we observed accumulation of Rad51p at a model hybrid-forming locus. Furthermore, we provide evidence that Rad51p mediates hybridization of transcripts to homologous chromosomal loci distinct from their site of synthesis. This hybrid formation in trans amplifies the genome-destabilizing potential of RNA and broadens the exclusive co-transcriptional models that pervade the field. The deleterious hybrid-forming activity of Rad51p is counteracted by Srs2p, a known Rad51p antagonist. Thus Srs2p serves as a novel anti-hybrid mechanism in vivo.

【 授权许可】

Unknown