Histone deposition and retention during DNA replication. (A) De novo histone H3.1-H4 deposition is initiated when new H3.1-H4 dimer precursors interact with the chaperone ASF1. ASF1 then hands them to the assembly factor CAF1 in complex with Rtt106. The (H3.1-H4)2 tetramer then forms and is deposited onto DNA via an interaction between CAF1 and the recruiter protein, proliferating cell nuclear antigen (PCNA). At the replication fork, FACT is associated with the minichromosome maintenance (MCM) complex to promote chromatin disassembly. Parental (H3.1-H4)2 tetramers are transferred behind the replication fork in a random fashion, possibly aided by FACT and ASF1. (B) During S phase, parental (CENP-A-H4)2 tetramers are depicted as being retained as intact molecules, consistent with the observed retention of preexisting CENP-A at replicated centromeres. The stability of CENP-A nucleosomes through multiple cell cycles is encoded within the CATD, through either the specific physical characteristics it confers or its interaction with an unknown factor. CENP-C binds to the C-terminal tail of CENP-A, further stabilizing the CENP-A nucleosome, which might be important for its retention through S phase.