DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (, ). In complex with CENPX (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM (, ). In complex with CENPX and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks . In complex with CENPT, CENPW and CENPX (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression . As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure (, ). DNA-binding function is fulfilled in the presence of CENPX, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own (, ).
Subcellular locations: Nucleus, Chromosome, Centromere, Chromosome, Centromere, Kinetochore
Assembly of CENPS and CENPX and its partner subunits CENPT and CENPW at centromeres occurs through a dynamic exchange mechanism. Although exchange is continuous in the cell cycle, de novo assembly starts principally during mid-late S phase and is complete by G2. CENPS is more stably bound at the kinetochore than CENPX (, ). During S phase, rapidly recruited to DNA interstrand cross-links that block replication . Recruited to DNA damage sites about 20 minutes following UV irradiation, reaching a plateau after approximately 40 minutes .
Ubiquitously expressed.