APCCdh1 controls cell cycle entry during liver regeneration

•Cdh1 expression is strongly reduced after PHx.•Cdh1 depletion prolongs S-phase in regenerating hepatocytes.•Loss of Cdh1 induces DNA damage responses in regenerating hepatocytes.

Cdh1 is one of the two adaptor proteins of anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase controlling mitosis and DNA replication. To date, the in vivo functions of Cdh1 have not been fully explored. In order to characterize Cdh1 in liver regeneration, we generated a conditional knock-out mouse model. Our data showed that loss of Cdh1 leads to increased and extended S phase progression possibly due to the upregulation of cyclin D1. Moreover, the increased DNA replication resulted in activated DNA damage response. Interestingly, the final liver weight after partial hepatectomy in the Cdh1 depleted mice did not differ from that of the controls, implying that Cdh1 is not required for the competence of hepatocytes to regenerate itself.