| Structural highlights
Disease
F111A_HUMAN Autosomal dominant Kenny-Caffey syndrome;Osteocraniostenosis. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
F111A_HUMAN Single-stranded DNA-binding serine protease that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:32165630). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:32165630). Protects replication fork from stalling by removing DPCs, such as covalently trapped topoisomerase 1 (TOP1) adducts on DNA lesion, or poly(ADP-ribose) polymerase 1 (PARP1)-DNA complexes trapped by PARP inhibitors (PubMed:32165630). Required for PCNA loading on replication sites (PubMed:24561620). Promotes S-phase entry and DNA synthesis (PubMed:24561620). Acts also as a restriction factor for some viruses including SV40 polyomavirus and vaccinia virus (PubMed:23093934, PubMed:37607234). Mechanistically, affects nuclear barrier function during viral replication by mediating the disruption of the nuclear pore complex (NPC) via its protease activity (PubMed:33369867, PubMed:37607234). In turn, interacts with vaccinia virus DNA-binding protein OPG079 in the cytoplasm and promotes its degradation without the need of its protease activity but through autophagy (PubMed:37607234).[1] [2] [3]
References
- ↑ Alabert C, Bukowski-Wills JC, Lee SB, Kustatscher G, Nakamura K, de Lima Alves F, Menard P, Mejlvang J, Rappsilber J, Groth A. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. Nat Cell Biol. 2014 Mar;16(3):281-93. PMID:24561620 doi:10.1038/ncb2918
- ↑ Kojima Y, Machida Y, Palani S, Caulfield TR, Radisky ES, Kaufmann SH, Machida YJ. FAM111A protects replication forks from protein obstacles via its trypsin-like domain. Nat Commun. 2020 Mar 12;11(1):1318. PMID:32165630 doi:10.1038/s41467-020-15170-7
- ↑ Zhu J, Gao X, Li Y, Zhang Z, Xie S, Ren S, Li Y, Li H, Niu K, Fu S, Deng Y, Li Y, Moss B, Wu W, Peng C. Human FAM111A inhibits vaccinia virus replication by degrading viral protein I3 and is antagonized by poxvirus host range factor SPI-1. Proc Natl Acad Sci U S A. 2023 Aug 29;120(35):e2304242120. PMID:37607234 doi:10.1073/pnas.2304242120
|
