title: Balancing eukaryotic replication asymmetry with replication fidelity.
abstract: Coordinated replication of eukaryotic nuclear genomes is asymmetric, with copying of a leading strand template preceding discontinuous copying of the lagging strand template. Replication is catalyzed by DNA polymerases α, δ and ɛ, enzymes that are related yet differ in physical and biochemical properties, including fidelity. Recent studies suggest that Pol ɛ is normally the primary leading strand replicase, whereas most synthesis by Pol δ occurs during lagging strand replication. New studies show that replication asymmetry can generate strand-specific genome instability resulting from biased deoxynucleotide pools and unrepaired ribonucleotides incorporated into DNA during replication, and that the eukaryotic replication machinery has evolved to most efficiently correct those replication errors that are made at the highest rates.
authors.affiliation: Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA. kunkel@niehs.nih.gov
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kunkel
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004256:DNA Polymerase I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004257:DNA Polymerase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004258:DNA Polymerase III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics*; D003854:Deoxyribonucleotides / Q000235:genetics / Q000378:metabolism*; D056890:Eukaryota; D042822:Genomic Instability; D006801:Humans; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D003854:Deoxyribonucleotides; D004247:DNA; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004258:DNA Polymerase III