A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining.
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A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining. / Grabarz, Anastazja ; Guirouilh-Barbat, Josée ; Barascu, Aurelia ; Pennarun, Gaëlle; Genet, Diane ; Rass, Emilie ; Germann, Susanne Manuela; Bertrand, Pascale ; Hickson, Ian David; Lopez, Bernard S. .
In: Cell Reports, Vol. 5, No. 1, 17.10.2013, p. 21-28.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining.
AU - Grabarz, Anastazja
AU - Guirouilh-Barbat, Josée
AU - Barascu, Aurelia
AU - Pennarun, Gaëlle
AU - Genet, Diane
AU - Rass, Emilie
AU - Germann, Susanne Manuela
AU - Bertrand, Pascale
AU - Hickson, Ian David
AU - Lopez, Bernard S.
PY - 2013/10/17
Y1 - 2013/10/17
N2 - The choice of the appropriate double-strand break (DSB) repair pathway isessential 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 anepistatic manner with 53BP1 and RIF1 and is required forionizing-radiation-induced 53BP1 focus assembly. Conversely, in the absence of53BP1 or RIF1, BLM promotes formation of A-EJ long deletions, consistent with arole 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/MRE11long-range deletions associated with A-EJ and (2) promotion of DNA resection.These antagonist roles can be regulated, according to cell-cycle stage, byinteracting partners such as 53BP1 and TopIII, to avoid unscheduled resectionthat might jeopardize genome integrity.
AB - The choice of the appropriate double-strand break (DSB) repair pathway isessential 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 anepistatic manner with 53BP1 and RIF1 and is required forionizing-radiation-induced 53BP1 focus assembly. Conversely, in the absence of53BP1 or RIF1, BLM promotes formation of A-EJ long deletions, consistent with arole 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/MRE11long-range deletions associated with A-EJ and (2) promotion of DNA resection.These antagonist roles can be regulated, according to cell-cycle stage, byinteracting partners such as 53BP1 and TopIII, to avoid unscheduled resectionthat might jeopardize genome integrity.
KW - Faculty of Health and Medical Sciences
KW - Center for Healthy Ageing
U2 - 10.1016/j.celrep.2013.08.034.
DO - 10.1016/j.celrep.2013.08.034.
M3 - Journal article
VL - 5
SP - 21
EP - 28
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 1
ER -
ID: 57286440