Chemical DNA damage activates p21 WAF1/CIP1-dependent intra-S checkpoint.
When cells progressing in G(1) phase are irradiated with UV light, two damage checkpoint pathways are activated: CHK1-Cdc25A and p53-p21WAF1/CIP1, both targeting Cdk2 but the latter inducing long lasting inactivation. In similarly irradiated S phase cells, however, p21WAF1/CIP1-dependent checkpoint is largely inactive. We report here that p21-dependent checkpoint can effectively be activated and induce a prolonged S phase arrest with similarly extended inactivation of Cdk2 by association of p21 if mid-S phase cells are damaged with a base-modifying agent instead of UV light, indicating that the poor utilization of p21-dependent checkpoint is not an innate property of S phase cells.
Kan
Qiuming
Q
Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Jinno
Shigeki
S
Yamamoto
Hanako
H
Okayama
Hiroto
H
D000818:Animals; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004249:DNA Damage; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D051379:Mice; D019000:Phosphotyrosine / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D051381:Rats; D016196:S Phase / Q000187:drug effects* / Q000528:radiation effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; D019000:Phosphotyrosine; D008741:Methyl Methanesulfonate; D051357:Cyclin-Dependent Kinase 2; D020687:cdc25 Phosphatases