6 Chromatin Assembly

Abstract

HISTONE SYNTHESIS AND DEPOSITION The DNA of all eukaryotic genomes is organized into a nucleoprotein complex called chromatin. Chromatin is essential for compacting genomic DNA and plays a primary role in governing DNA accessibility and gene expression. The composition of chromatin is modulated during all DNA transactions, including DNA replication, transcription, repair, and recombination. Therefore, the formation, maintenance, and alterations of chromatin structures are of central importance to eukaryotic molecular biology. Nucleosomes are the fundamental, repeating subunits of chromatin. Nucleosomes contain an octamer of core histone proteins, two molecules each of histones H2A, H2B, H3, and H4, around which 146 bp of DNA wraps 1.7 times (Luger et al. 1997). When the genomic DNA is duplicated during each S phase of the cell cycle, metazoan cells must make millions of new nucleosomes to accommodate the new DNA. Histone deposition occurs almost immediately onto newly synthesized DNA (for review, see Franco and Kaufman 2004; Loyola and Almouzni 2004; Gunjan et al. 2005). This coordination between DNA synthesis and nucleosome formation during S phase is essential for eukaryotic organisms to avoid DNA damage and replication fork collapse (Hoek and Stillman 2003; Ye et al. 2003; Franco et al. 2005; Groth et al. 2005). However, not all nucleosome formation occurs in concert with replication; histones are mobilized and/or evicted from DNA during many other chromosomal transactions, including transcription and DNA repair. Therefore, histone deposition onto DNA must occur both during and outside of S phase, and both these processes affect genome stability. Regulation...