TY - JOUR
T1 - Neocarzinostatin-induced Rad51 nuclear focus formation is cell cycle regulated and aberrant in AT cells
AU - Yuan, Shyng Shiou F.
AU - Yang, Yuan Kai
AU - Chen, Hsiao Wen
AU - Chung, Yueh Fang
AU - Chang, Hsueh Ling
AU - Su, Jinn Huang
PY - 2003/11/1
Y1 - 2003/11/1
N2 - DNA double-stranded breaks are the most detrimental form of DNA damage and, if not repaired properly, may lead to an accumulation of chromosomal aberrations and eventually tumorigenesis. Proteins of the Rad51/Rad52 epitasis group are crucial for the recombinational repair of DNA double-stranded breaks, whereas the Rad50/NBS1/Mre11 nuclease complex is involved in both the recombinational and the end-joining repair of DNA double-stranded breaks. Herein, we demonstrate that the chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not NBS1, nuclear focus formation in a cell- cycle-dependent manner. Furthermore, neocarzinostatin-induced Rad51 foci formation revealed a slower kinetic change in AT cells, but not in wild-type or NBS cells. In summary, our results suggest that neocarzinostatin induces Rad51 focus formation through an ATM- and cell-cycle-dependent, but NBS1-independent, pathway.
AB - DNA double-stranded breaks are the most detrimental form of DNA damage and, if not repaired properly, may lead to an accumulation of chromosomal aberrations and eventually tumorigenesis. Proteins of the Rad51/Rad52 epitasis group are crucial for the recombinational repair of DNA double-stranded breaks, whereas the Rad50/NBS1/Mre11 nuclease complex is involved in both the recombinational and the end-joining repair of DNA double-stranded breaks. Herein, we demonstrate that the chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not NBS1, nuclear focus formation in a cell- cycle-dependent manner. Furthermore, neocarzinostatin-induced Rad51 foci formation revealed a slower kinetic change in AT cells, but not in wild-type or NBS cells. In summary, our results suggest that neocarzinostatin induces Rad51 focus formation through an ATM- and cell-cycle-dependent, but NBS1-independent, pathway.
KW - DNA double-stranded breaks
KW - End-joining
KW - Neocarzinostatin
KW - Nuclear focus formation
KW - Recombinational repair
UR - http://www.scopus.com/inward/record.url?scp=0142185102&partnerID=8YFLogxK
U2 - 10.1016/S0041-008X(03)00013-9
DO - 10.1016/S0041-008X(03)00013-9
M3 - 文章
C2 - 14575640
AN - SCOPUS:0142185102
SN - 0041-008X
VL - 192
SP - 231
EP - 236
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -