PT  - JOURNAL ARTICLE
AU  - Rios-Szwed, Diana O
AU  - Alvarez, Vanesa
AU  - Sanchez-Pulido, Luis
AU  - Garcia-Wilson, Elisa
AU  - Jiang, Hao
AU  - Bandau, Susanne
AU  - Lamond, Angus
AU  - Alabert, Constance
TI  - FAM111A regulates replication origin activation and cell fitness
AID  - 10.26508/lsa.202302111
DP  - 2023 Dec 01
TA  - Life Science Alliance
PG  - e202302111
VI  - 6
IP  - 12
4099  - http://www.life-science-alliance.org/content/6/12/e202302111.short
4100  - http://www.life-science-alliance.org/content/6/12/e202302111.full
SO  - Life Sci. Alliance2023 Dec 01; 6
AB  - FAM111A is a replisome-associated protein and dominant mutations within its trypsin-like peptidase domain are linked to severe human developmental syndrome, the Kenny–Caffey syndrome. However, FAM111A functions remain unclear. Here, we show that FAM111A facilitates efficient activation of DNA replication origins. Upon hydroxyurea treatment, FAM111A-depleted cells exhibit reduced single-stranded DNA formation and a better survival rate. Unrestrained expression of FAM111A WT and patient mutants causes accumulation of DNA damage and cell death, only when the peptidase domain remains intact. Unrestrained expression of FAM111A WT also causes increased single-stranded DNA formation that relies on S phase entry, FAM111A peptidase activity but not its binding to proliferating cell nuclear antigen. Altogether, these data unveil how FAM111A promotes DNA replication under normal conditions and becomes harmful in a disease context.