Interaction between DNA-dependent protein kinase and a novel protein, KIP

被引:58
作者
Wu, XT
Lieber, MR
机构
[1] WASHINGTON UNIV,SCH MED,DEPT PATHOL,DIV MOL ONCOL,ST LOUIS,MO 63110
[2] WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOL BIOPHYS,DIV MOL ONCOL,ST LOUIS,MO 63110
来源
MUTATION RESEARCH-DNA REPAIR | 1997年 / 385卷 / 01期
关键词
DNA dependent protein kinase; scid; double-strand break repair; V(D)J recombination;
D O I
10.1016/S0921-8777(97)00035-9
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
DNA-dependent protein kinase (DNA-PKcs) is the only eukaryotic kinase activated by DNA ends. Mutation of DNA-PKcs results in murine severe combined immune deficiency in mice and radiation sensitivity, Both the immune and the radiation defects are due to a failure in double-strand break repair. Biochemical studies indicate that DNA-PKcs kinase activity is simulated by the presence of the DNA end binding protein, Ku. Autophosphorylation of DNA-PKcs results in its inactivation. Based on these studies, DNA-PKcs is presumed to play a direct and important role in the repair of double-strand breaks, but the details of its role are quite unclear. We have done two-hybrid analysis of this entire protein to identify other proteins with which it interacts. Thus far, extensive analysis has only revealed one strong interaction that satisfies both high genetic and biochemical stringency. The interaction is with a novel human protein that has 26% amino acid identity with the phosphatase component, calcineurin B. We discuss the interaction of DNA-PKcs with this novel calcium-binding protein family member in the context of possible kinase-photophatase regulation of DNA end joining. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:13 / 20
页数:8
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