A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 04 2022
19 04 2022
Historique:
received:
16
04
2021
accepted:
25
03
2022
entrez:
20
4
2022
pubmed:
21
4
2022
medline:
22
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35440629
doi: 10.1038/s41467-022-29629-2
pii: 10.1038/s41467-022-29629-2
pmc: PMC9019021
doi:
Substances chimiques
Chromatin
0
RNA
63231-63-0
DNA
9007-49-2
RecQ Helicases
EC 3.6.4.12
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2012Informations de copyright
© 2022. The Author(s).
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