Title : Carcinogen-induced S-phase arrest is Chk1 mediated and caffeine sensitive.

Pub. Date : 2002 Feb

PMID : 11864911






9 Functional Relationships(s)
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Protein Name
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1 The checkpoint kinase Chk1 (but not Chk2) was phosphorylated after treatment with low doses of BPDE. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
2 High concentrations of BPDE elicited phosphorylation of both Chk1 and Chk2. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
3 Adenovirus-mediated expression of "dominant-negative" Chk1 (but not dominant-negative Chk2) and the Chk1 inhibitor UCN-01 abrogated the S-phase delay elicited by low doses of BPDE. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
4 Adenovirus-mediated expression of "dominant-negative" Chk1 (but not dominant-negative Chk2) and the Chk1 inhibitor UCN-01 abrogated the S-phase delay elicited by low doses of BPDE. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
5 Consistent with a role for the caffeine-sensitive ATM or ATR protein kinase in low-dose BPDE-induced S-phase arrest, both Chk1 phosphorylation and S-phase arrest were abrogated by caffeine. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
6 However, low doses of BPDE elicited Chk1 phosphorylation and S-phase arrest in AT cells (from ataxia telangiectasia patients), demonstrating that ATM is dispensable for S-phase checkpoint responses to this genotoxin. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
7 BPDE-induced Chk1 phosphorylation and S-phase arrest were abrogated by caffeine treatment in AT cells, suggesting that a caffeine-sensitive kinase other than ATM is an important mediator of responses to BPDE-adducted DNA. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
8 BPDE-induced Chk1 phosphorylation and S-phase arrest were abrogated by caffeine treatment in AT cells, suggesting that a caffeine-sensitive kinase other than ATM is an important mediator of responses to BPDE-adducted DNA. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens
9 Overall, our data demonstrate the existence of a caffeine-sensitive, Chk1-mediated, S-phase checkpoint that is operational in response to BPDE. 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide checkpoint kinase 1 Homo sapiens