CAF1

CAF1, or Chromatin Assembly Factor 1, is a conserved histone chaperone complex that mediates replication-coupled nucleosome assembly. Its primary role is to deposit histone H3-H4 onto newly synthesized DNA behind the replication fork, helping to restore or maintain chromatin structure during S phase and after DNA repair.

The complex is typically a heterotrimer composed of three subunits. In humans, these are CHAF1A (p150), CHAF1B (p60), and CHAF1C (p48). In budding yeast, the orthologs are Cac1 (p150), Cac2 (p60), and Cac3 (p48). The large subunit, particularly the p150/Cac1 component, contains a PCNA-interacting peptide (PIP) motif that couples CAF1 activity to the replication machinery via PCNA. The subunits work together to form a functional chaperone that accepts H3-H4 dimers, often in coordination with another histone chaperone such as ASF1, and delivers them to nascent DNA.

Functionally, CAF1 is involved not only in DNA replication but also in chromatin reassembly after DNA damage, contributing to genome stability and the maintenance of higher-order chromatin structures, including heterochromatin and transcriptional silencing at certain loci. Its activity is coordinated with other chromatin regulators and is subject to cell-cycle–dependent regulation, with disruptions leading to replication stress and genomic instability.

Clinically, altered CAF1 subunit expression or function has been observed in various cancers and remains an area of investigation for understanding replication-associated chromatin dynamics and potential therapeutic targeting. CAF1 is an essential, evolutionarily conserved component of the chromatin assembly machinery.