Claspin is involved in S-phase checkpoint induced by benzo(a)pyrene in 16HBE cells.
Environmental carcinogen benzo(a)pyrene (BaP) can damage DNA by forming bulky adducts that are degraded further to DNA strand breaks, thus contributing to induce DNA damage checkpoint response. Claspin is a critical checkpoint protein in response to multiple forms of genotoxic stress including UV, IR and hydroxyurea (HU). In the present study we have investigated the role of human Claspin in the DNA damage checkpoint elicited by BaP in 16HBE cells. We observed that Claspin levels are increased in a time-dependent manner in response to S-phase arrest induced by BaP. In addition, the levels of phosphorylation of Chk1 on S345 were increased, but the levels of Cdc25A were decreased after treatment with BaP. Inhibition of Claspin expression (siRNA) attenuated the effect of BaP on S-phase arrest and abrogated the activation of Chk1 and degradation of Cdc25A in response to BaP. Taken together, these data imply that Claspin plays an important role in S-phase checkpoint induced by BaP, and it participates in the activation of Chk1 and Cdc25A in this checkpoint pathway.
Qi
Yanmin
Y
Department of Toxicology, Peking University Health Science Center, Beijing 100083, PR China.
Zhao
Peng
P
Fu
Juanling
J
Yao
Biyun
B
Yuan
Zhun
Z
Hu
Entan
E
Zhou
Zongcan
Z
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002460:Cell Line; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; C488158:CLSPN protein, human; D002274:Carcinogens, Environmental; D001564:Benzo(a)pyrene; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases