Regulation and functional contribution of thymidine kinase 1 in repair of DNA damage.

ABSTRACT: Cellular supply of dNTPs is essential in the DNA replication and repair processes. Here we investigated the regulation of thymidine kinase 1 (TK1) in response to DNA damage and found that genotoxic insults in tumor cells cause up-regulation and nuclear localization of TK1. During recovery from DNA damage, TK1 accumulates in p53-null cells due to a lack of mitotic proteolysis as these cells are arrested in the G(2) phase by checkpoint activation. We show that in p53-proficient cells, p21 expression in response to DNA damage prohibits G(1)/S progression, resulting in a smaller G(2) fraction and less TK1 accumulation. Thus, the p53 status of tumor cells affects the level of TK1 after DNA damage through differential cell cycle control. Furthermore, it was shown that in HCT-116 p53(-/-) cells,

SUBMITTER: Chen YL 

PROVIDER: S-EPMC2930731 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature