TY - JOUR T1 - FAM111A regulates replication origin activation and cell fitness JF - bioRxiv DO - 10.1101/2020.04.22.055574 SP - 2020.04.22.055574 AU - Diana O. Rios-Szwed AU - Elisa Garcia-Wilson AU - Luis Sanchez-Pulido AU - Vanesa Alvarez AU - Hao Jiang AU - Susanne Bandau AU - Angus Lamond AU - Chris P. Ponting AU - Constance Alabert Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/23/2020.04.22.055574.abstract N2 - FAM111A is a replisome associated protein and dominant mutations within its trypsin-like peptidase domain are linked to severe human developmental syndromes. However, FAM111A functions and its putative substrates remain largely unknown. Here, we showed that FAM111A promotes origin activation and interacts with the putative peptidase FAM111B, and we identified the first potential FAM111A substrate, the suicide enzyme HMCES. Moreover, unrestrained expression of FAM111A wild-type and patient mutants impaired DNA replication and caused cell death only when the peptidase domain remained intact. Altogether our data reveal how FAM111A promotes DNA replication in normal conditions and becomes harmful in a disease context.Competing Interest StatementThe authors have declared no competing interest. ER -