ASF1A
Function
Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly (PubMed:10759893, PubMed:11897662, PubMed:12842904, PubMed:14718166, PubMed:15664198, PubMed:16151251, PubMed:21454524). Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly (PubMed:11897662, PubMed:14718166, PubMed:15664198). Promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks: acts by mediating histone replacement at DSBs, leading to recruitment of the MMS22L-TONSL complex and subsequent loading of RAD51 (PubMed:29478807). Also involved in the nuclear import of the histone H3-H4 dimer together with importin-4 (IPO4): specifically recognizes and binds newly synthesized histones with the monomethylation of H3 'Lys-9' and acetylation at 'Lys-14' (H3K9me1K14ac) marks, and diacetylation at 'Lys-5' and 'Lys-12' of H4 (H4K5K12ac) marks in the cytosol (PubMed:21454524, PubMed:29408485). Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit (PubMed:15621527).
Post-translational modifications
Phosphorylated by TLK1 and TLK2 (PubMed:11470414, PubMed:20016786, PubMed:35136069). Highly phosphorylated in S-phase and at lower levels in M-phase (PubMed:11470414). TLK2-mediated phosphorylation at Ser-192 prevents proteasome-dependent degradation (PubMed:20016786). Phosphorylation at Ser-192 by PRKDC in response to DNA damage promotes the histone chaperone activity and ability to replace histones at double-strand breaks (DSBs) at stalled or collapsed replication forks, leading to RAD51 recruitment (PubMed:29478807).
Sequence Similarities
Belongs to the ASF1 family.
Tissue Specificity
Ubiquitously expressed.
Cellular localization
- Nucleus
- Chromosome
Alternative names
CGI-98, HSPC146, ASF1A, Histone chaperone ASF1A, Anti-silencing function protein 1 homolog A, CCG1-interacting factor A, hAsf1, hAsf1a, CIA, hCIA