PT  - JOURNAL ARTICLE
AU  - S Cohen
AU  - A Guenolé
AU  - A Marnef
AU  - T Clouaire
AU  - N Puget
AU  - V Rocher
AU  - C Arnould
AU  - M Aguirrebengoa
AU  - M Genais
AU  - D Vernekar
AU  - R Mourad
AU  - V Borde
AU  - G Legube
TI  - BLM-dependent Break-Induced Replication handles DSBs in transcribed chromatin upon impaired RNA:DNA hybrids dissolution
AID  - 10.1101/2020.05.13.093112
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.13.093112
4099  - http://biorxiv.org/content/early/2020/05/15/2020.05.13.093112.short
4100  - http://biorxiv.org/content/early/2020/05/15/2020.05.13.093112.full
AB  - Transcriptionally active loci are particularly prone to breakage and mounting evidence suggest that DNA Double-Strand Breaks arising in genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loops accumulation and dissolution. Here, we uncovered a critical function of the Bloom RecQ DNA helicase (BLM) in TC-DSBR in human cells. BLM is recruited in a transcription dependent-manner at DSBs where it fosters resection, RAD51 binding and accurate Homologous Recombination repair. However, in a R-loop dissolution-deficient background BLM switches from promoting Homologous Recombination to promoting Break-Induced Replication (BIR), which strongly impairs cell viability. Altogether our work unveils a role for BLM in BIR at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at these transcription-associated DSBs.Competing Interest StatementThe authors have declared no competing interest.