Arsenic-induced Mre11 phosphorylation is cell cycle-dependent and defective in NBS cells.
Cancer-prone diseases ataxia-telangiectasia (AT), Nijmegen breakage syndrome (NBS) and ataxia-telangiectasia-like disorder (ATLD) are defective in the repair of DNA double-stranded break (DSB). On the other hand, arsenic (As) has been reported to cause DSB and to be involved in the occurrence of skin, lung and bladder cancers. To dissect the repair mechanism of As-induced DSB, wild type, AT and NBS cells were treated with sodium arsenite to study the complex formation and post-translational modification of Rad50/NBS1/Mre11 repair proteins. Our results showed that Mre11 went through cell cycle-dependent phosphorylation upon sodium arsenite treatment and this post-translational modification required NBS1 but not ATM. Defective As-induced Mre11 phosphorylation was rescued by reconstitution with full length NBS1 in NBS cells. Although As-induced Mre11 phosphorylation was not required for Rad50/NBS1/Mre11 complex formation, it might be required for the formation of Rad50/NBS1/Mre11 nuclear foci upon DNA damage.
Yuan
Shyng-Shiou F
SS
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan ROC. yuanssf@ms33.hinet.net
Su
Jinu-Huang
JH
Hou
Ming-Feng
MF
Yang
Fei-Wen
FW
Zhao
Song
S
Lee
Eva Y-H P
EY
D018053:Arsenites / Q000633:toxicity*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D017670:Sodium Compounds / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D018053:Arsenites; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017670:Sodium Compounds; C017947:sodium arsenite; D004247:DNA; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae