Details

Autor(en) / Beteiligte

• Cohen, S
• Guenolé, A
• Lazar, I
• Marnef, A
• Clouaire, T
• Vernekar, D V
• Puget, N
• Rocher, V
• Arnould, C
• Aguirrebengoa, M
• Genais, M
• Firmin, N
• Shamanna, R A
• Mourad, R
• Bohr, V A
• Borde, V
• Legube, G

Titel

A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation

Ist Teil von

• Nature communications, 2022-04, Vol.13 (1), p.2012-2012, Article 2012

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Transcriptionally active loci are particularly prone to breakage and mounting evidence suggests that DNA Double-Strand Breaks arising in active genes are handled by a dedicated repair pathway, Transcription-Coupled DSB Repair (TC-DSBR), that entails R-loop accumulation and dissolution. Here, we uncover a function for 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 an R-loop dissolution-deficient background, we find that BLM promotes cell death. We report that upon excessive RNA:DNA hybrid accumulation, DNA synthesis is enhanced at DSBs, in a manner that depends on BLM and POLD3. Altogether our work unveils a role for BLM at DSBs in active chromatin, and highlights the toxic potential of RNA:DNA hybrids that accumulate at transcription-associated DSBs.