Abstract
The advance of replication forks to duplicate chromosomes in dividing cells requires the disassembly of nucleosomes ahead of the fork and the rapid assembly of parental and de novo histones at the newly synthesized strands behind the fork. Replication-coupled chromatin assembly provides a unique opportunity to regulate fork advance and stability. Through post-translational histone modifications and tightly regulated physical and genetic interactions between chromatin assembly factors and replisome components, chromatin assembly: (1) controls the rate of DNA synthesis and adjusts it to histone availability; (2) provides a mechanism to protect the integrity of the advancing fork; and (3) regulates the mechanisms of DNA damage tolerance in response to replication-blocking lesions. Uncoupling DNA synthesis from nucleosome assembly has deleterious effects on genome integrity and cell cycle progression and is linked to genetic diseases, cancer, and aging.
Highlights
Chromosome duplication during cell division has to accurately maintain the genetic and epigenetic information written in the chromatin
Human FACT promotes the unwinding activity of the Mcm2-7 helicase on nucleosomal templates in vitro [50], suggesting that it could directly disassemble nucleosomes ahead of the fork to facilitate DNA synthesis during replication. Another factor involved in recycling parental histones is Asf1, a conserved histone chaperone first described in yeast for its function in heterochromatin silencing [53] and later purified from Drosophila as a replication-coupled assembly factor (RCAF) [54]
An integrative view of DNA replication cannot be presented without taking into consideration the process of nucleosome assembly
Summary
Chromosome duplication during cell division has to accurately maintain the genetic and epigenetic information written in the chromatin. A major source of genetic and epigenetic instability is generated during the advance of the replication fork, a dynamic nucleosome-free structure with single-stranded DNA (ssDNA) gaps and DNA ends susceptible to being aberrantly processed. These fragile structures have to deal with a number of obstacles such as DNA adducts, abasic sites, DNA-binding proteins and specific DNA and chromatin structures that hamper their advance and compromise their stability, and are controlled by the replication checkpoint to ensure their correct progression and stability. We refer the readers to recent reviews for more detailed analyses of the mechanisms of chromatin assembly, with discussions on the biological functions of canonical and histone variants [7,8,9,10]
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