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DOI | 10.1126/science.aak9654 |
DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair | |
Sibanda, Bancinyane L.1; Chirgadze, Dimitri Y.1; Ascher, David B.1,2; Blundell, Tom L.1 | |
2017-02-03 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 355期号:6324页码:520-+ |
文章类型 | Article |
语种 | 英语 |
国家 | England; Australia |
英文摘要 | DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a central component of nonhomologous end joining (NHEJ), repairing DNA double-strand breaks that would otherwise lead to apoptosis or cancer. We have solved its structure in complex with the C-terminal peptide of Ku80 at 4.3 angstrom resolution using x-ray crystallography. We show that the 4128-amino acid structure comprises three large structural units: the N-terminal unit, the Circular Cradle, and the Head. Conformational differences between the two molecules in the asymmetric unit are correlated with changes in accessibility of the kinase active site, which are consistent with an allosteric mechanism to bring about kinase activation. The location of KU80ct(194) in the vicinity of the breast cancer 1 (BRCA1) binding site suggests competition with BRCA1, leading to pathway selection between NHEJ and homologous recombination. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000393183100044 |
WOS关键词 | DEPENDENT PROTEIN-KINASE ; CATALYTIC SUBUNIT ; 3-DIMENSIONAL STRUCTURE ; CELL-CYCLE ; DOMAIN ; COMPLEX ; KU ; AUTOPHOSPHORYLATION ; RECOMBINATION ; DEFICIENCY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/195357 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Cambridge, Dept Biochem, Old Addenbrookes Site,80 Tennis Court Rd, Cambridge CB2 1GA, England; 2.Univ Melbourne, Dept Biochem & Mol Biol, 30 Flemington Rd, Parkville, Vic 3052, Australia |
推荐引用方式 GB/T 7714 | Sibanda, Bancinyane L.,Chirgadze, Dimitri Y.,Ascher, David B.,et al. DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair[J]. SCIENCE,2017,355(6324):520-+. |
APA | Sibanda, Bancinyane L.,Chirgadze, Dimitri Y.,Ascher, David B.,&Blundell, Tom L..(2017).DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair.SCIENCE,355(6324),520-+. |
MLA | Sibanda, Bancinyane L.,et al."DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair".SCIENCE 355.6324(2017):520-+. |
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