A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Anastazja Grabarz, Josée Guirouilh-Barbat, Aurelia Barascu, Gaëlle Pennarun, Diane Genet, Emilie Rass, Susanne Manuela Germann, Pascale Bertrand, Ian David Hickson, Bernard S. Lopez

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.
OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind5
Udgave nummer1
Sider (fra-til)21-28
Antal sider8
DOI
StatusUdgivet - 17 okt. 2013

ID: 57286440