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How RNA transcripts coordinate DNA recombination and repair

Shane McDevitt, Timur Rusanov, Tatiana Kent, Gurushankar Chandramouly and Richard T. Pomerantz ()
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Shane McDevitt: Temple University Lewis Katz School of Medicine
Timur Rusanov: Temple University Lewis Katz School of Medicine
Tatiana Kent: Temple University Lewis Katz School of Medicine
Gurushankar Chandramouly: Temple University Lewis Katz School of Medicine
Richard T. Pomerantz: Temple University Lewis Katz School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Genetic studies in yeast indicate that RNA transcripts facilitate homology-directed DNA repair in a manner that is dependent on RAD52. The molecular basis for so-called RNA−DNA repair, however, remains unknown. Using reconstitution assays, we demonstrate that RAD52 directly cooperates with RNA as a sequence-directed ribonucleoprotein complex to promote two related modes of RNA−DNA repair. In a RNA-bridging mechanism, RAD52 assembles recombinant RNA−DNA hybrids that coordinate synapsis and ligation of homologous DNA breaks. In an RNA-templated mechanism, RAD52-mediated RNA−DNA hybrids enable reverse transcription-dependent RNA-to-DNA sequence transfer at DNA breaks that licenses subsequent DNA recombination. Notably, we show that both mechanisms of RNA−DNA repair are promoted by transcription of a homologous DNA template in trans. In summary, these data elucidate how RNA transcripts cooperate with RAD52 to coordinate homology-directed DNA recombination and repair in the absence of a DNA donor, and demonstrate a direct role for transcription in RNA−DNA repair.

Date: 2018
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DOI: 10.1038/s41467-018-03483-7

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