Dimerization-dependent serine protease activity of FAM111A prevents replication fork stalling at topoisomerase 1 cleavage complexes

• Published in: Nature communications Vol. 15; no. 1; pp. 2064 - 16
• Main Authors: Palani, Sowmiya, Machida, Yuka, Alvey, Julia R., Mishra, Vandana, Welter, Allison L., Cui, Gaofeng, Bragantini , Benoît, Botuyan, Maria Victoria, Cong, Anh T. Q., Mer, Georges, Schellenberg, Matthew J., Machida, Yuichi J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.03.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337/1427/1979; 631/45/173; 631/535/1266; 82/16; 82/80; 82/83; Antiviral drugs; BASIC BIOLOGICAL SCIENCES; Chymotrypsin; Cleavage; Crystal defects; Deoxyribonucleic acid; Dimerization; DNA; DNA adducts; DNA biosynthesis; DNA damage; DNA Replication; DNA topoisomerase; Enzyme mechanisms; Enzymes; Genetic disorders; Humanities and Social Sciences; Missense mutation; Molecular structure; multidisciplinary; Mutagenesis; Mutation; Peptides; Protease; Proteins; Proteolysis; Replication; Science; Science & Technology; Science (multidisciplinary); Serine; Serine Endopeptidases - metabolism; Serine Proteases; Serine proteinase; Stalling; Substrates; X-ray crystallography; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46207-w

FAM111A, a serine protease, plays roles in DNA replication and antiviral defense. Missense mutations in the catalytic domain cause hyper-autocleavage and are associated with genetic disorders with developmental defects. Despite the enzyme’s biological significance, the molecular architecture of the...