Neocarzinostatin induces Mre11 phosphorylation and focus formation through an ATM- and NBS1-dependent mechanism.
DNA double-strand breaks, if unrepaired, may lead to the accumulation of chromosomal aberrations and eventually cancer cell formation. Components of the Rad50/NBS/Mre11 nuclease complex are essential for the effective repair of DNA double-stranded breaks. Here, we show that neocarzinostatin, a radiomimetic enediyne antibiotic, induces phosphorylation and nuclear focus formation of Mre11 and NBS1 through a cell cycle-independent mechanism. Furthermore, neocarzinostatin-induced Mre11 phosphorylation and nuclear focus formation are defective in AT and NBS cells, but not wild type cells. Our results suggest that ATM and NBS1 are required for the effective repair of neocarzinostatin-induced DNA double-strand breaks by both non-homologous end joining and homologous recombinational repair pathways.
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC. yuanssf@ms33.hinet.net
Shyng Shiou F
SS
Yuan
Hsueh Ling
HL
Chang
Ming Feng
MF
Hou
Te Fu
TF
Chan
Ying Hsien
YH
Kao
Yang Chang
YC
Wu
Jinu Huang
JH
Su
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D009353:Zinostatin / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D009353:Zinostatin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae