A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining.
Research output: Contribution to journal › Journal article › Research › peer-review
Anastazja Grabarz, Josée Guirouilh-Barbat, Aurelia Barascu, Gaëlle Pennarun, Diane Genet, Emilie Rass, Susanne Manuela Germann, Pascale Bertrand, Ian David Hickson, Bernard S. Lopez
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.
|Number of pages||8|
|Publication status||Published - 17 Oct 2013|
- Faculty of Health and Medical Sciences