CENPS

CENPS was identified in the neuroblastoma tumor suppressor candidate region on chromosome 1p36. It contains a TFIID-31 domain, similar to that found in TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription

Full Name

Centromere Protein S

Function

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 (PubMed:20347428, PubMed:20347429).
In complex with CENPX (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM (PubMed:20347428, PubMed:20347429).
In complex with CENPX and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks (PubMed:20347428).
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 (PubMed:19620631).
As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure (PubMed:20347428, PubMed:22304917).
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 (PubMed:20347428, PubMed:20347429).

Biological Process

Cell division Source: UniProtKB-KW
Cellular response to DNA damage stimulus Source: UniProtKB
CENP-A containing nucleosome assembly Source: Reactome
DNA repair Source: UniProtKB
Interstrand cross-link repair Source: Reactome
Kinetochore assembly Source: InterPro
Mitotic spindle organization Source: Reactome
Positive regulation of protein ubiquitination Source: UniProtKB
Replication fork processing Source: UniProtKB
Resolution of meiotic recombination intermediates Source: UniProtKB

Cellular Location

Nucleus; 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 (PubMed:19620631, PubMed:24522885). During S phase, rapidly recruited to DNA interstrand cross-links that block replication (PubMed:20347428). Recruited to DNA damage sites about 20 minutes following UV irradiation, reaching a plateau after approximately 40 minutes (PubMed:24522885).