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bioRxiv · 10.1101/2021.04.23.440542

RAP80 suppresses the vulnerability of R-loops during DNA double-strand break repair

Yasuhara, T.·Kato, R.·Yamauchi, M.·Uchihara, Y.·Zou, L.·Miyagawa, K.·Shibata, A.
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Abstract

R-loops, consisting of ssDNA and DNA-RNA hybrids, are potentially vulnerable unless they are appropriately processed. Recent evidence suggests that R-loops can form in the proximity of DNA double-strand breaks (DSBs) within transcriptionally active regions. Yet, how the vulnerability of R-loops is overcome during DSB repair remains unclear. Here, we identify RAP80 as a factor suppressing the vulnerability of ssDNA in R-loops and chromosome translocations and deletions during DSB repair. Mechanistically, RAP80 prevents unscheduled nucleolytic processing of ssDNA in R-loops by CtIP. This mechanism promotes efficient DSB repair via transcription-associated end-joining dependent on BRCA1, Pol{theta}, and LIG1/3. Thus, RAP80 suppresses the vulnerability of R-loops during DSB repair, thereby precluding genomic abnormalities in a critical component of the genome caused by deleterious R-loop processing.

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Yasuhara, T., Kato, R., Yamauchi, M., Uchihara, Y., Zou, L., Miyagawa, K., Shibata, A.. 2021-04-24. RAP80 suppresses the vulnerability of R-loops during DNA double-strand break repair. https://doi.org/10.1101/2021.04.23.440542

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