FAM111A regulates replication origin activation and cell fitness
Diana O. Rios-Szwed,
Chris P Ponting,
Posted 23 Apr 2020
bioRxiv DOI: 10.1101/2020.04.22.055574
Posted 23 Apr 2020
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 Statement The authors have declared no competing interest.
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