Structure-Function Studies Of DNA Replication Fidelity

今年，我们发表了六项与DNA复制保真度相关的初步研究。一项研究表明，在酵母DNA前导链和后链复制过程中，dNTP池失衡对复制不忠的促进作用大致相同。另一项研究表明，最近发现的Prim-Pol酶进行翻译DNA合成。我们发现组蛋白H2A的沉积。Z通过SWR-C重塑酶防止基因组不稳定。我们对DNA聚合酶mu进行了结构-功能研究，表明它具有独特的能力，仅在短间隙内使用5 '模板核苷酸进行DNA合成。最后，我们对酵母DNA复制过程中核糖核苷酸的掺入进行了两项研究。一项研究推断了真核生物三种主要复制酶在前导链和滞后链复制中的作用。另一项研究表明，短重复DNA序列的缺失是由于拓扑异构酶1在前导链复制过程中切割DNA聚合酶epsilon结合的核糖核苷酸的DNA骨干，而不是由于Pol δ或Pol α在后导链复制过程中切割结合的核糖核苷酸。

This year we published six primary studies related to DNA replication fidelity. One study showed that dNTP pool imbalances promote replication infidelity in yeast approximately equally well during leading and lagging strand DNA replication. Another study showed that the recently discovered enzyme Prim-Pol conducts translesion DNA synthesis. We showed that deposition of histone H2A.Z by the SWR-C remodeling enzyme prevents genome instability. We performed a structure-function study of DNA polymerase mu showing that it has the unique ability to conduct DNA synthesis using only the 5-prime template nucleotide in a short gap. Lastly, we conducted two studies of ribonucleotide incorporation during DNA replication in yeast. One study inferred the roles of the three major eukaryotic replicases in leading and lagging strand replication. The other study indicated that deletions of short repetitive DNA sequences result from topoisomerase 1 cleavage of the DNA backbone at ribonucleotides incorporated by DNA polymerase epsilon during leading strand replication, but not by cleavage at ribonucleotides incorporated during lagging strand replication by Pol delta or Pol alpha.