How to fix DNA breaks: new insights into the mechanism of non-homologous end joining

被引:4
|
作者
Vogt, Alex [1 ,2 ]
He, Yuan [1 ,2 ,3 ,4 ]
Lees-Miller, Susan P. [5 ,6 ]
机构
[1] Northwestern Univ, Dept Mol Biosci, Evanston, IL USA
[2] Northwestern Univ, Interdisciplinary Biol Sci Program, Evanston, IL USA
[3] Northwestern Univ, Chem Life Proc Inst, Evanston, IL USA
[4] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA
[5] Univ Calgary, Dept Biochem & Mol Biol, Robson DNA Sci Ctr, Calgary, AB T2N 4N1, Canada
[6] Univ Calgary, Arnie Charbonneau Canc Inst, Calgary, AB T2N 4N1, Canada
关键词
DEPENDENT PROTEIN-KINASE; DOUBLE-STRAND BREAK; CRYO-EM STRUCTURE; CATALYTIC SUBUNIT; CRYSTAL-STRUCTURE; STRUCTURAL INSIGHTS; REPAIR; PKCS; AUTOPHOSPHORYLATION; COMPLEX;
D O I
10.1042/BST20220741
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing radiation-induced DNA double-strand breaks (DSBs) in human cells and is essential for the generation of mature T and B cells in the adaptive immune system via the process of V(D) J recombination. Here, we review how recently determined structures shed light on how NHEJ complexes function at DNA DSBs, emphasizing how multiple structures containing the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) may function in NHEJ. Together, these studies provide an explanation for how NHEJ proteins assemble to detect and protect DSB ends, then proceed, through DNA-PKcs-dependent autophosphorylation, to a ligation-competent complex.
引用
收藏
页码:1789 / 1800
页数:12
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