Linkage Between DNA Repair and Chromatin Modification

1. Linkage Between DNA Repair and Chromatin Modification

2. Biochemical experiments have permitted the identification of acidic factors that can form complexes with histones and enhance the process of histone deposition. They act as histone chaperones by facilitating the formation of nucleosome cores without being part of the final reaction product. These histone-interacting factors, also called chromatin-assembly factors (CAF), can bind preferentially to a subset of histone proteins. Chromatin Assembly Factor-1 (CAF-1) interacts with newly synthesized acetylated histones H3 and H4 to preferentially assemble chromatin during DNA replication. CAF-1 is also capable of promoting the assembly of chromatin specifically coupled to the repair of DNA. The recent demonstration of the interaction of CAF-1 with the protein Proliferating Cell Nuclear Antigen (PCNA) established a molecular link between the assembly of chromatin and the processes of replication and repair of DNA. PCNA function can be regulated by the binding of several proteins including p21, MCMT, XPG, p33ING1b, FEN1, and the growth arrest after DNA damage (GADD45) proteins. They have in common a PCNA-Interacting-Protein Domain (PIP) consisting of Qxxhxxaa where Q is glutamine, x is any amino acid, h is a hydrophobic amino acid and a is an aromatic amino acid. P33ING1b in particular binds to PCNA in a uv-inducible manner and recruits different HAT complexes to the site of replication/repair therefore functionally bridging DNA repair and chromatin modification. Adapted from Feng X. et al Trends in Cell Biology 12:532, 2002. Linkage Between DNA Repair and Chromatin Modification