Chromatin replication Sample Clauses

Chromatin replication. In vivo, DNA in the nuclei of cells is packaged into a structure called chromatin. Thus, chromatin is the natural substrate for processes such as replication and transcription. The fundamental repeating unit of eukaryotic chromatin is the nucleosome, which is composed of two copies each of four (positively-charged) histone proteins: H2A, H2B, H3, and H4. These are wrapped around roughly 147 bp of DNA. The inherent stability of nucleosomes provides an opportunity to store information at specific positions in the genome in the form of covalent histone modifications. Importantly, the histone proteins and any modifications they contain must be replicated in each S-phase along with the DNA. The disruption of the chromatin landscape during replication provides an opportunity to change (or maintain) specific histone modifications. Such replication-induced alterations can change the transcriptional state of a cell (Xxxxxxx and Xxxxx, 2013). However, relatively little is known about how the replication machinery interacts with chromatin. The coupling of DNA replication to nucleosome assembly is important as impaired nucleosome assembly in humans can destabilise replication forks, and eventually give rise to damage and genomic instability (Xxxxx et al. 2007; Xxxxxxxxx and Xxxxx, 2004; Xxxx and Xxxxxxxx, 2003; Xxxxxxxx et al. 2014; Ye et al. 2003). One mechanism that has been proposed in recent years involves nucleosome assembly on the lagging strand (Xxxxxxx et al. 2017; Xxxxx et al. 2017; Xxxxxxxxxxx et al. 2017; Xxxxx and Xxxxxxxxxx, 2012). In this model, nucleosomes are formed on Okazaki fragments as they are sufficiently elongated by DNA polymerase δ. Intriguingly, it has been pointed out that the size of an Okazaki fragment is roughly the size of a nucleosome repeat (approximately 200 bp in humans) (Xxxxxxx et al. 2017). It was demonstrated previously that Fen1 and DNA ligase I are able to function in a chromatin environment in S. cerevisiae (Xxxxxx et al. 2000; Xxxxxxx et al.
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