Homologous Recombination and the Formation of Complex Genomic Rearrangements

被引:66
|
作者
Piazza, Aurele [1 ,3 ]
Heyer, Wolf-Dietrich [1 ,2 ]
机构
[1] Univ Calif Davis, Dept Microbiol & Mol Genet, Davis, CA 95616 USA
[2] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA
[3] Inst Pasteur, CNRS, Spatial Regulat Genomes, Dept Genomes & Genet,Unite Mixte Rech 3525, F-75015 Paris, France
基金
美国国家卫生研究院;
关键词
BREAK-INDUCED REPLICATION; DOUBLE HOLLIDAY JUNCTIONS; CHROMOSOME-PULVERIZATION; HALF-CROSSOVERS; DNA-POLYMERASE; MPH1; HELICASE; D-LOOPS; REPAIR; RAD51; YEAST;
D O I
10.1016/j.tcb.2018.10.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The maintenance of genome integrity involves multiple independent DNA damage avoidance and repair mechanisms. However, the origin and pathways of the focal chromosomal reshuffling phenomena collectively referred to as chromothripsis remain mechanistically obscure. We discuss here the role, mechanisms, and regulation of homologous recombination (HR) in the formation of simple and complex chromosomal rearrangements. We emphasize features of the recently characterized multi-invasion (MI)-induced rearrangement (MIR) pathway which uniquely amplifies the initial DNA damage. HR intermediates and cellular contexts that endanger genomic stability are discussed as well as the emerging roles of various classes of nucleases in the formation of genome rearrangements. Long-read sequencing and improved mapping of repeats should enable better appreciation of the significance of recombination in generating genomic rearrangements.
引用
收藏
页码:135 / 149
页数:15
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