Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks

被引：402

作者：

Chan, DW

Chen, BPC

Prithivirajsingh, S

Kurimasa, A

Story, MD

Qin, J

Chen, DJ ^{[1
]}

机构：

[1] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA

[2] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[4] Univ Texas, MD Anderson Canc Ctr, Dept Expt Radiotherapy, Houston, TX 77030 USA

来源：

GENES & DEVELOPMENT | 2002年 / 16卷 / 18期

关键词：

nonhomologous end-joining; DNA damage response; autophosphorylation; DNA-PK; DNA-PKcs; Ku; radiation sensitivity; ionizing radiation;

D O I：

10.1101/gad.1015202

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

Nonhomologous end-joining (NHEJ) is the predominant pathway that repairs DNA double-strand breaks (DSBs) in mammalian cells. The DNA-dependent protein kinase (DNA-PK), consisting of Ku and DNA-PK catalytic subunit (DNA-PKcs), is activated by DNA in vitro and is required for NHEJ. We report that DNA-PKcs is auto-phosphorylated at Thr2609 in vivo in a Ku-dependent manner in response to ionizing radiation. Phosphorylated DNA-PKcs colocalizes with both gamma-H2AX and 53BP1 after DNA damage. Mutation of Thr2609 to Ala leads to radiation sensitivity and impaired DSB rejoining. These findings establish that Ku-dependent phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by NHEJ.

引用

页码：2333 / 2338

页数：6

共 33 条

[1]

Enhanced phosphorylation of p53 by ATN in response to DNA damage [J].