Figure 1.
Working model of nucleosome disruption and restoration.
Minichromosome maintenance (MCM2-7) proteins, as part of the replication fork progression complex, mediate DNA unwinding and coordinate nucleosome disruption in a step by step manner. The FACT complex is recruited to peel off H2A–H2B, exposing the H4 C-terminal tail and creating a platform for Asf1, which lands and triggers the disruption of the parental tetramer. The histone H3 binding activity of Mcm2 could aid the disruption, and participates in holding histones until they are transferred onto the daughter strands. Additional factors may participate in disruption and transfer. On nascent DNA, nucleosome assembly occurs in a stepwise fashion, with the deposition of (H3–H4)2, followed by the addition of 2 H2A–H2B dimmers. CAF-1 mediates the deposition of new H3–H4 dimers via recruitment to PCNA, and Asf1, as a coordinator of histone provision, aids this process, likely by donating histones to CAF-1. NAP1 brings in new histone H2A–H2B, and possibly old H2A–H2B, made available from transcriptional exchange. Image reproduced from Groth (2009) with permission from NRC Research Press.