Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends

被引：135

作者：

Guirouilh-Barbat, Jose ^{[1
]}

Rass, Emilie ^{[1
]}

Plo, Isabelle ^{[1
]}

Bertrand, Pascale ^{[1
]}

Lopez, Bernard S. ^{[1
]}

机构：

[1] Ctr Natl Rech Sci Commissariat Energie Atom, Inst Radiobiol Cell Mol, Commiss Energie Atom, Unit mixte Rech 217, F-92265 Fontenay Aux Roses, France

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 52期

关键词：

double-strand break repair; genome rearrangements;

D O I：

10.1073/pnas.0708541104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

XRCC4-null mice have a more severe phenotype than KU80-null mice. Here, we address whether this difference in phenotype is connected to nonhomologous end-joining (NHEJ). We used intrachromosomal substrates to monitor NHEJ of two distal double-strand breaks (DSBs) targeted by I-Scel, in living cells. In xrcc4-defective XR-1 cells, a residual but significant end-joining process exists, which primarily uses microhomologies distal from the DSB. However, NHEJ efficiency was strongly reduced in xrcc4-defective XR-1 cells versus complemented cells, contrasting with KU-deficient xrs6 cells, which showed levels of end-joining similar to those of complemented cells. Nevertheless, sequence analysis of the repair junctions indicated that the accuracy of end-joining was strongly affected in both xrcc4-deficient and KU-deficient cells. More specifically, these data showed that the KU80/XRCC4 pathway is conservative and not intrinsically error-prone but can accommodate non-fully complementary ends at the cost of limited mutagenesis.

引用

页码：20902 / 20907

页数：6

共 47 条

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