Branchpoint translocation by fork remodelers as a general mechanism of R-loop removal.
Cell Rep
; 41(10): 111749, 2022 12 06.
Article
in En
| MEDLINE
| ID: mdl-36476850
ABSTRACT
Co-transcriptional R loops arise from stalling of RNA polymerase, leading to the formation of stable DNARNA hybrids. Unresolved R loops promote genome instability but are counteracted by helicases and nucleases. Here, we show that branchpoint translocases are a third class of R-loop-displacing enzyme in vitro. In cells, deficiency in the Fanconi-anemia-associated branchpoint translocase FANCM causes R-loop accumulation, particularly after treatment with DNARNA-hybrid-stabilizing agents. This correlates with FANCM localization at R-loop-prone regions of the genome. Moreover, other branchpoint translocases associated with human disease, such as SMARCAL1 and ZRANB3, and those from lower organisms can also remove R loops in vitro. Branchpoint translocases are more potent than helicases in resolving R loops, indicating their evolutionary important role in R-loop suppression. In human cells, FANCM, SMARCAL1, and ZRANB3 depletion causes additive effects on R-loop accumulation and DNA damage. Our work reveals a mechanistic basis for R-loop displacement that is linked to genome stability.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA
/
R-Loop Structures
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2022
Type:
Article
Affiliation country:
Australia