RRC ID |
62562
|
著者 |
Imamichi S, Sharma MK, Kamdar RP, Fukuchi M, Matsumoto Y.
|
タイトル |
Ionizing radiation-induced XRCC4 phosphorylation is mediated through ATM in addition to DNA-PK.
|
ジャーナル |
Proc Jpn Acad Ser B Phys Biol Sci
|
Abstract |
XRCC4 (X-ray cross-complementation group 4) is a protein associated with DNA ligase IV, which is thought to join two DNA ends at the final step of DNA double-strand break repair through non-homologous end-joining. It has been shown that, in response to irradiation or treatment with DNA damaging agents, XRCC4 undergoes phosphorylation, requiring DNA-PK. Here we explored possible role of ATM, which is structurally related to DNA-PK, in the regulation of XRCC4. The radiosensitizing effects of DNA-PK inhibitor and/or ATM inhibitor were dependent on XRCC4. DNA-PK inhibitor and ATM inhibitor did not affect the ionizing radiation-induced chromatin recruitment of XRCC4. Ionizing radiation-induced phosphorylation of XRCC4 in the chromatin-bound fraction was largely inhibited by DNA-PK inhibitor but further diminished by the combination with ATM inhibitor. The present results indicated that XRCC4 phosphorylation is mediated through ATM as well as DNA-PK, although DNA-PK plays the major role. We would propose a possible model that DNA-PK and ATM acts in parallel upstream of XRCC4, regulating through phosphorylation.
|
巻・号 |
90(9)
|
ページ |
365-72
|
公開日 |
2014-1-1
|
DOI |
10.2183/pjab.90.365
|
PII |
DN/JST.JSTAGE/pjab/90.365
|
PMID |
25391321
|
PMC |
PMC4324928
|
MeSH |
Animals
Ataxia Telangiectasia Mutated Proteins / metabolism
Binding Sites
Cell Line, Tumor
Cell Survival
Chromatin / metabolism
DNA / radiation effects*
DNA Breaks, Double-Stranded
DNA Damage
DNA Repair
DNA-Activated Protein Kinase / metabolism*
DNA-Binding Proteins / metabolism*
Enzyme Inhibitors / metabolism
Mice
Nuclear Proteins / metabolism*
Phosphorylation
Radiation, Ionizing
|
IF |
3.0
|
リソース情報 |
ヒト・動物細胞 |
M10(RCB0136) |