Role of inhibitory CDC2 phosphorylation in radiation-induced G2 arrest in human cells
- PMID: 8769420
- PMCID: PMC2120957
- DOI: 10.1083/jcb.134.4.963
Role of inhibitory CDC2 phosphorylation in radiation-induced G2 arrest in human cells
Abstract
The activity of the mitosis-promoting kinase CDC2-cyclin B is normally suppressed in S phase and G2 by inhibitory phosphorylation at Thr14 and Tyr15. This work explores the possibility that these phosphorylations are responsible for the G2 arrest that occurs in human cells after DNA damage. HeLa cell lines were established in which CDC2AF, a mutant that cannot be phosphorylated at Thr14 and Tyr15, was expressed from a tetracycline-repressible promoter. Expression of CDC2AF did not induce mitotic events in cells arrested at the beginning of S phase with DNA synthesis inhibitors, but induced low levels of premature chromatin condensation in cells progressing through S phase and G2. Expression of CDC2AF greatly reduced the G2 delay that resulted when cells were X-irradiated in S phase. However, a significant G2 delay was still observed and was accompanied by high CDC2-associated kinase activity. Expression of wild-type CDC2, or the related kinase CDK2AF, had no effect on the radiation-induced delay. Thus, inhibitory phosphorylation of CDC2, as well as additional undefined mechanisms, delay mitosis after DNA damage.
Similar articles
-
Nuclear localization of cyclin B1 controls mitotic entry after DNA damage.J Cell Biol. 1998 May 18;141(4):875-85. doi: 10.1083/jcb.141.4.875. J Cell Biol. 1998. PMID: 9585407 Free PMC article.
-
The role of Cdc2 feedback loop control in the DNA damage checkpoint in mammalian cells.Cancer Res. 1997 Nov 15;57(22):5168-78. Cancer Res. 1997. PMID: 9371520
-
S and G2 phase roles for Cdk2 revealed by inducible expression of a dominant-negative mutant in human cells.Mol Cell Biol. 2001 Apr;21(8):2755-66. doi: 10.1128/MCB.21.8.2755-2766.2001. Mol Cell Biol. 2001. PMID: 11283255 Free PMC article.
-
[The characterization of human cdc2 kinase and CDK2].Yakugaku Zasshi. 1993 Dec;113(12):829-46. doi: 10.1248/yakushi1947.113.12_829. Yakugaku Zasshi. 1993. PMID: 8301538 Review. Japanese.
-
Regulation of the G2/M transition by p53.Oncogene. 2001 Apr 5;20(15):1803-15. doi: 10.1038/sj.onc.1204252. Oncogene. 2001. PMID: 11313928 Review.
Cited by
-
The lifetime of the oxygen-evolving complex subunit PSBO depends on light intensity and carbon availability in Chlamydomonas.Plant Cell Environ. 2023 Feb;46(2):422-439. doi: 10.1111/pce.14481. Epub 2022 Nov 17. Plant Cell Environ. 2023. PMID: 36320098 Free PMC article.
-
Meiotic DNA replication checkpoint control in fission yeast.Genes Dev. 1999 Oct 1;13(19):2581-93. doi: 10.1101/gad.13.19.2581. Genes Dev. 1999. PMID: 10521402 Free PMC article.
-
Checkpoint defects leading to premature mitosis also cause endoreplication of DNA in Aspergillus nidulans.Mol Biol Cell. 1999 Nov;10(11):3661-74. doi: 10.1091/mbc.10.11.3661. Mol Biol Cell. 1999. PMID: 10564263 Free PMC article.
-
MPF localization is controlled by nuclear export.EMBO J. 1998 Jul 15;17(14):4127-38. doi: 10.1093/emboj/17.14.4127. EMBO J. 1998. PMID: 9670027 Free PMC article.
-
The SFP1 gene product of Saccharomyces cerevisiae regulates G2/M transitions during the mitotic cell cycle and DNA-damage response.Genetics. 1998 Dec;150(4):1419-28. doi: 10.1093/genetics/150.4.1419. Genetics. 1998. PMID: 9832520 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous