N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku

被引：26

作者：

Meek, Katheryn ^{[1
,2
]}

Lees-Miller, Susan P. ^{[3
,4
]}

Modesti, Mauro ^{[5
]}

机构：

[1] Michigan State Univ, Dept Microbiol & Mol Genet, Coll Vet Med, E Lansing, MI 48824 USA

[2] Michigan State Univ, Dept Pathobiol & Diagnost Invest, Coll Vet Med, E Lansing, MI 48824 USA

[3] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada

[4] Univ Calgary, Dept Oncol, Calgary, AB T2N 4N1, Canada

[5] Aix Marseille Univ, Lab Genome Instabil & Carcinogenesis, Unite Propre Rech 3081, CNRS, F-13402 Marseille 20, France

来源：

NUCLEIC ACIDS RESEARCH | 2012年 / 40卷 / 07期

关键词：

STRAND BREAK REPAIR; V(D)J RECOMBINATION; PHOSPHORYLATION SITES; AUTOPHOSPHORYLATION; PK; ENDS; REQUIREMENT; RADIATION; SYNAPSIS; PATHWAY;

D O I：

10.1093/nar/gkr1211

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：

The DNA-dependent protein kinase (DNA-PK) was identified as an activity and as its three component polypeptides 25 and 15 years ago, respectively. It has been exhaustively characterized as being absolutely dependent on free double stranded DNA ends (to which it is directed by its regulatory subunit, Ku) for its activation as a robust nuclear serine/threonine protein kinase. Here, we report the unexpected finding of robust DNA-PKcs activation by N-terminal constraint, independent of either DNA or its regulatory subunit Ku. These data suggest that an N-terminal conformational change (likely induced by DNA binding) induces enzymatic activation.

引用

收藏

页码：2964 / 2973

页数：10

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