A role for BLM in double-strand break repair pathway choice: prevention of CtIP/Mre11-mediated alternative nonhomologous end-joining.
Cell Rep
; 5(1): 21-8, 2013 Oct 17.
Article
in En
| MEDLINE
| ID: mdl-24095737
ABSTRACT
The choice of the appropriate double-strand break (DSB) repair pathway is essential for the maintenance of genomic stability. Here, we show that the Bloom syndrome gene product, BLM, counteracts CtIP/MRE11-dependent long-range deletions (>200 bp) generated by alternative end-joining (A-EJ). BLM represses A-EJ in an epistatic manner with 53BP1 and RIF1 and is required for ionizing-radiation-induced 53BP1 focus assembly. Conversely, in the absence of 53BP1 or RIF1, BLM promotes formation of A-EJ long deletions, consistent with a role for BLM in DSB end resection. These data highlight a dual role for BLM that influences the DSB repair pathway choice (1) protection against CtIP/MRE11 long-range deletions associated with A-EJ and (2) promotion of DNA resection. These antagonist roles can be regulated, according to cell-cycle stage, by interacting partners such as 53BP1 and TopIII, to avoid unscheduled resection that might jeopardize genome integrity.
Full text:
1
Database:
MEDLINE
Main subject:
Nuclear Proteins
/
Carrier Proteins
/
DNA-Binding Proteins
/
RecQ Helicases
/
DNA Breaks, Double-Stranded
/
DNA End-Joining Repair
Limits:
Humans
Language:
En
Year:
2013
Type:
Article