title: Eukaryotic genome instability in light of asymmetric DNA replication.
abstract: The eukaryotic nuclear genome is replicated asymmetrically, with the leading strand replicated continuously and the lagging strand replicated as discontinuous Okazaki fragments that are subsequently joined. Both strands are replicated with high fidelity, but the processes used to achieve high fidelity are likely to differ. Here we review recent studies of similarities and differences in the fidelity with which the three major eukaryotic replicases, DNA polymerases α, δ, and ɛ, replicate the leading and lagging strands with high nucleotide selectivity and efficient proofreading. We then relate the asymmetric fidelity at the replication fork to the efficiency of DNA mismatch repair, ribonucleotide excision repair and topoisomerase 1 activity.
authors.affiliation: a Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Lujan
authors.affiliation: a Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Williams
authors.affiliation: a Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences , Research Triangle Park , NC , USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
mesh_terms: D020137:Base Pair Mismatch; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D042822:Genomic Instability
chemical_list: D004259:DNA-Directed DNA Polymerase
keywords: DNA mismatch repair; exonucleolytic proofreading; genomic ribonucleotide; mutation; polymerase; replication fork
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