Abstract
DNA replication is a complex process that needs to be executed accurately before cell division in order to maintain genome integrity. DNA replication is divided into three main stages: initiation, elongation and termination. One of the key events during initiation is the assembly of the replicative helicase at origins of replication, and this mechanism has been very well described over the last decades. In the last six years however, researchers have also focused on deciphering the molecular mechanisms underlying the disassembly of the replicative helicase during termination. Similar to replisome assembly, the mechanism of replisome disassembly is strictly regulated and well conserved throughout evolution, although its complexity increases in higher eukaryotes. While budding yeast rely on just one pathway for replisome disassembly in S phase, higher eukaryotes evolved an additional mitotic pathway over and above the default S phase specific pathway. Moreover, replisome disassembly has been recently found to be a key event prior to the repair of certain DNA lesions, such as under-replicated DNA in mitosis and inter-strand cross-links (ICLs) in S phase. Although replisome disassembly in human cells has not been characterised yet, they possess all of the factors involved in these pathways in model organisms, and de-regulation of many of them are known to contribute to tumorigenesis and other pathological conditions.
Highlights
Genome replication is a highly regulated and co-ordinated process that our cells need to complete before undergoing cell division
In the last six years biochemistry and cell biology research carried out using Saccharomyces cerevisiae, Xenopus laevis egg extract and Caenorhabditis elegans embryos has allowed us to draw the first model of the mechanism of eukaryotic DNA replication termination
Chromosome replication starts from origins of replication, which are the genomic locations where loading and activation of the replicative helicases takes place resulting in double-stranded DNA unwinding and exposure of single-stranded DNA templates for DNA synthesis
Summary
DNA replication is a complex process that needs to be executed accurately before cell division in order to maintain genome integrity. One of the key events during initiation is the assembly of the replicative helicase at origins of replication, and this mechanism has been very well described over the last decades. In the last six years researchers have focused on deciphering the molecular mechanisms underlying the disassembly of the replicative helicase during termination. The mechanism of replisome disassembly is strictly regulated and well conserved throughout evolution, its complexity increases in higher eukaryotes. Replisome disassembly has been recently found to be a key event prior to the repair of certain DNA lesions, such as under-replicated DNA in mitosis and inter-strand cross-links (ICLs) in S phase. Replisome disassembly in human cells has not been characterised yet, they possess all of the factors involved in these pathways in model organisms, and de-regulation of many of them are known to contribute to tumorigenesis and other pathological conditions
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