Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability

• DOI: 10.1101/gad.1322905
• Publication Date: 2005-08-15T19:02:44Z
• Authors: Po-Yuan Ke; Yuan-Yeh Kuo; Chuan-Mei Hu; Zee-Fen Chang
• Keywords: Anaphase-promoting complex; CDC20; Mitotic exit

Anaphase promoting complex/cyclosome (APC/C)-mediated proteolysis is essential for chromosome segregation, mitotic exit, and G1 entry. Here, we show the importance of APC/C in control dTTP pool size mammalian cells. Two enzymes, thymidine kinase 1 (TK1) thymidylate (TMPK), involved formation are targets pathway. We demonstrate that TMPK recognized degraded by APC/C–Cdc20/Cdh1-mediated pathways from mitosis to early phase, whereas TK1 targeted degradation APC/C–Cdh1 after exit. Overexpression wild-type induces a four- fivefold increase cellular without spontaneous mutations hprt ( hypoxanthine-guanine phosphoribosyl transferase ) gene. In contrast, coexpression nondegradable expands 10-fold accompanied drastic dNTP imbalance. Most interestingly, disruption leads growth retardation striking gene mutation rate. conclude down-regulation pathway during phase an means maintain balanced avoid genetic instability.