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

Citations Over TimeTop 10% of 2013 papers

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.

Related Papers

• → Gene Targeting in Aspergillus fumigatus by Homologous Recombination Is Facilitated in a Nonhomologous End- Joining-Deficient Genetic Background(2006)301 cited
• → Aging impairs double-strand break repair by homologous recombination inDrosophilagerm cells(2016)45 cited
• → Quality control of homologous recombination(2014)36 cited
• → The MRE11-RAD50-XRS2 Complex, in Addition to Other Non-homologous End-joining Factors, Is Required for V(D)J Joining in Yeast(2005)21 cited
• → Homologous recombination and nonhomologous end-joining repair in yeast(2021)1 cited