Cyclin A2 as a regulator of DNA strand stability (1047.6)

Cyclin A2 regulates replication origin firing during S-phase. It binds to Cdk1 and Cdk2 to direct phosphorylation of proteins for DNA synthesis. The goals of this study were to determine the role of Cyclin A2 in the prevention of DNA double strand breaks (DSB). We deleted Cyclin A2 in mouse neural stem cells (NSC) using a cre/lox approach. Cyclin A2-null NSC showed increased BrdU incorporation, as well as increased staining for the mitotic marker pH3. However, the growth rate in these Cyclin A2-null cells was slowed. To explain this discordance, we examined the DSB marker γH2AX. Cyclin A2-null NSC show increased levels of γH2AX as compared to Cyclin A2-preserved cells. When a DSB forms, the cell cycle is arrested until the break is repaired. Rad51, a marker of homologous recombination repair, and 53BP1, a marker of non-homologous end joining, both localized to the site of DSB in Cyclin A2-null cells. This indicates that Cyclin A2-null NSC can repair these breaks. Our results suggest that Cyclin A2 does no...