DNA double-strand break repair pathways, chromosomal rearrangements and cancer

被引:87
作者
Kasparek, Torben R. [1 ]
Humphrey, Timothy C. [1 ]
机构
[1] Univ Oxford, CRUK MRC Gray Inst Radiat Oncol & Biol, Dept Oncol, Oxford OX1 2JD, England
基金
英国医学研究理事会;
关键词
DNA double-strand break; Homologous recombination; Non-homologous end joining; Chromosomal rearrangement; Cancer; NEARBY INVERTED REPEATS; END-JOINING REPAIR; GENE CONVERSION; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; GENOME INSTABILITY; MULTIPLE PATHWAYS; INDUCED REPLICATION; SEQUENCING REVEALS;
D O I
10.1016/j.semcdb.2011.10.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chromosomal rearrangements, which can lead to oncogene activation and tumour suppressor loss, are a hallmark of cancer cells. Such outcomes can result from both the repair and misrepair of DNA ends, which arise from a variety of lesions including DNA double strand breaks (DSBs), collapsed replication forks and dysfunctional telomeres. Here we review the mechanisms by which non-homologous end joining (NHEJ) and homologous recombination (HR) repair pathways can both promote chromosomal rearrangements and also suppress them in response to such lesions, in accordance with their increasingly recognised tumour suppressor function. Further, we consider how chromosomal rearrangements, together with a modular approach towards understanding their etiology, may be exploited for cancer therapy. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:886 / 897
页数:12
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