Involvement of DNA-dependent Protein Kinase in Normal Cell Cycle Progression through Mitosis

被引：70

作者：

Lee, Kyung-Jong ^{[1
]}

Lin, Yu-Fen ^{[1
]}

Chou, Han-Yi ^{[2
]}

Yajima, Hirohiko ^{[1
]}

Fattah, Kazi R. ^{[1
]}

Lee, Sheng-Chung ^{[2
]}

Chen, Benjamin P. C. ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Div Mol Radiat Biol, Dept Radiat Oncol, Dallas, TX 75390 USA

[2] Natl Taiwan Univ, Inst Mol Med, Coll Med, Taipei 10051, Taiwan

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 14期

基金：

美国国家卫生研究院; 美国国家航空航天局;

关键词：

DOUBLE-STRAND BREAK; INDUCED REPLICATION STRESS; CATALYTIC SUBUNIT; PHOSPHORYLATION SITES; KINETOCHORE CAPTURE; MITOTIC SPINDLE; IN-VIVO; CHECKPOINT; DAMAGE; LOCALIZATION;

D O I：

10.1074/jbc.M110.212969

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 catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) plays an important role in DNA double-strand break (DSB) repair as the underlying mechanism of the non-homologous end joining pathway. When DSBs occur, DNA-PKcs is rapidly phosphorylated at both the Thr-2609 and Ser-2056 residues, and such phosphorylations are critical for DSB repair. In this study we report that, in addition to responding to DSBs, DNA-PKcs is activated and phosphorylated in normal cell cycle progression through mitosis. Mitotic induction of DNA-PKcs phosphorylation is closely associated with the spindle apparatus at centrosomes and kinetochores. Furthermore, depletion of DNA-PKcs protein levels or inhibition of DNA-PKcs kinase activity results in the delay of mitotic transition because of chromosome misalignment. These results demonstrate for the first time that DNA-PKcs, in addition to its role in DSB repair, is a critical regulator of mitosis and could modulate microtubule dynamics in chromosome segregation.

引用

页码：12796 / 12802

页数：7

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