平衡真核复制的不对称性与复制保真度。
Balancing eukaryotic replication asymmetry with replication fidelity.
机构信息
Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
出版信息
Curr Opin Chem Biol. 2011 Oct;15(5):620-6. doi: 10.1016/j.cbpa.2011.07.025. Epub 2011 Aug 19.
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.
摘要
真核生物核基因组的复制是不对称的，先导链模板的复制先于滞后链模板的不连续复制。复制由 DNA 聚合酶 α、δ 和 ε 催化，这些酶虽然相关，但在物理和生化性质上存在差异，包括保真度。最近的研究表明，Pol ɛ 通常是主要的先导链复制酶，而 Pol δ 的大部分合成发生在滞后链复制过程中。新的研究表明，复制不对称性会导致由脱氧核苷酸池偏倚和复制过程中未修复的核糖核苷酸掺入 DNA 引起的链特异性基因组不稳定性，并且真核复制机制已经进化到能够最有效地纠正那些以最高速率发生的复制错误。
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