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，在领先和滞后链DNA复制期间，dNTP池失衡促进了酵母中的复制不保真性。另一项研究表明，最近发现的酶Prim-Pol进行跨病变DNA合成。我们表明，SWR-C重塑酶沉积组蛋白H2A.Z可以防止基因组的不稳定性。我们对DNA聚合酶Mu进行了结构-功能研究，表明它具有在短时间内仅用5个碱基的模板核苷酸进行DNA合成的独特能力。最后，我们对酵母DNA复制过程中的核糖核苷酸掺入进行了两项研究。一项研究推断了三种主要的真核复制酶在领先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DNA聚合酶epsilon在先导链复制过程中加入的核糖核酸处的DNA骨架的拓扑异构酶1裂解，而不是由于Pol Delta或POLα在滞后链复制过程中加入的核糖核苷酸的裂解所致。

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.