RT Journal Article
SR Electronic
T1 BLM-dependent Break-Induced Replication handles DSBs in transcribed chromatin upon impaired RNA:DNA hybrids dissolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.13.093112
DO 10.1101/2020.05.13.093112
A1 S Cohen
A1 A Guenolé
A1 A Marnef
A1 T Clouaire
A1 N Puget
A1 V Rocher
A1 C Arnould
A1 M Aguirrebengoa
A1 M Genais
A1 D Vernekar
A1 R Mourad
A1 V Borde
A1 G Legube
YR 2020
UL http://biorxiv.org/content/early/2020/05/15/2020.05.13.093112.abstract
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.