Regulation of DNA replication by chromatin structures: accessibility and recruitment

Abstract

The initiation of DNA replication and the elongation of DNA strands take place in chromatin, a huge compound DNA-protein complex. Although the factors involved in the process of DNA replication have been largely elucidated, the underlying mechanisms that determine their behavior in the context of chromatin have only recently begun to be understood. It has been known that transcription is tightly regulated by the state of chromatin compaction, which governs the accessibility of DNA to trans-acting factors. This process is influenced by several determinants of chromatin structure, including intrinsic nucleosome positioning, the nucleosome remodeling complex, histone post-translational modifiers, and histone- and DNA-binding proteins. Growing evidence indicates that this concept is also applicable to the regulation of DNA replication. In addition, recent studies have demonstrated a distinctive mode of regulation. Some non-histone chromatin-binding proteins have been shown to interact physically with replication factors, thereby facilitating their recruitment at specific chromosomal loci. This type of regulation may allow control of local replication activity without affecting other chromosomal processes.