Parental histone recycling Sample Clauses

Parental histone recycling. Early experiments using phage T4 replication proteins and SV40 minichromosomes in human cell extracts revealed that nucleosomes ahead of the replication fork do not dissociate from and remain bound to replicated DNA (Xxxxx-Xxxxxx et al. 1990; Xxxxx and Xxxxxxxx 1991; Xxxxxxx and Xxxxx, 1992). It was also shown that these nucleosomes are rapidly re-assembled and dispersed to both of the daughter strands in vivo (XxXxxxxx and Xxxxxx, 1977; Xxxxxx et al. 1984; Xxxx et al. 1986). However, it remained unclear as to how the replisome is able to progress through nucleosome-bound DNA. Recent breakthroughs in the field have revealed that replication through chromatinised templates in vitro requires several proteins in addition to those needed to replicate naked DNA (Kurat et al. 2017). These minimally include the histone chaperones facilitates chromatin transcription (FACT) and non-histone protein 6 (Nhp6), though other proteins can enhance replication through chromatin, including acetyltransferases and ATP- dependent nucleosome spacing factors such as imitation switch subfamily 1a (ISW1a) and inositol requiring 80 (INO80) (Kurat et al. 2017). Together, these proteins allow the replisome to achieve in vivo replication rates through chromatin in vitro (Xxxxx et al. 2017). However, it remains unclear how these proteins promote replication in the context of chromatin. FACT is essential in S. cerevisiae and has been shown to be a part of the RPC (Xxxxxx et al. 2006). It has also been shown to interact with both histones H3-H4 and H2A-H2B (Formosa, 2011; Xxxxxxx et al. 2011). It has been proposed to act either in front of the replisome, where it could play a role in disassembling nucleosomes ahead of the replication fork, or behind the replisome, where it could help to deposit parental nucleosomes on the nascent DNA (Xxxxx et al. 2017). It is possible that it acts in both capacities, and it may have other as yet undiscovered roles in chromatin replication. Nhp6 is required at much higher concentrations, suggesting that it may act distributivity as opposed to travelling with the replication fork (Kurat et al. 2017). INO80 has been shown to alter the position of nucleosomes around replication forks, though it is unclear how (or if) it is targeted to replication forks during S-phase (Xxx et al. 2015). Furthermore, replication through chromatin in this in vitro system resulted in the recycling of parental nucleosomes on the nascent DNA (Kurat et al. 2017). It was previously...
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