Human DNA polymerase η accommodates RNA for strand extension
Human DNA polymerase η accommodates RNA for strand extension
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DOI：
10.1074/jbc.m117.809723
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发表时间：
2017-11-03
影响因子：
4.8
通讯作者：
Guengerich, F. Peter
中科院分区：
文献类型：
--
作者：
Su, Yan;Egli, Martin;Guengerich, F. Peter
核糖核苷酸是脱氧核糖核苷酸的天然类似物，它可能被 DNA 聚合酶错误插入，导致基因组中最丰富的 DNA 损伤。在复制过程中，DNA 聚合酶不同程度地耐受亲本链上的核糖核苷酸片段。据报道，大多数人类 DNA 聚合酶都会将核糖核苷酸错误地插入基因组中。然而，只有 PrimPol、DNA 聚合酶、端粒酶和线粒体人类 DNA 聚合酶 (hpol) 已被证明可以耐受整个 RNA 链。 Y 家族 hpol 因与紫外线诱导的 DNA 损伤环丁烷嘧啶二聚体相对的跨损伤合成而闻名，并且最近被发现可将核糖核苷酸掺入 DNA 中。在这里，我们报告 hpol 能够以相似的亲和力结合 DNA/DNA、RNA/DNA 和 DNA/RNA 双链体。此外， hpol 以及另一种 Y 家族 DNA 聚合酶 hpol 在引物延伸过程中将 RNA 作为两条链之一，主要是通过在未修饰的模板或 DNA 损伤对面插入 dNMP，例如 8-氧代-2-脱氧鸟苷或环丁烷嘧啶二聚体，即使存在等量的 DNA/DNA 底物。 hpol这种RNA调节能力的发现重新定义了人类DNA聚合酶的传统概念，并表明了hpol在体内潜在的新功能。
Ribonucleotides are the natural analogs of deoxyribonucleotides, which can be misinserted by DNA polymerases, leading to the most abundant DNA lesions in genomes. During replication, DNA polymerases tolerate patches of ribonucleotides on the parental strands to different extents. The majority of human DNA polymerases have been reported to misinsert ribonucleotides into genomes. However, only PrimPol, DNA polymerase , telomerase, and the mitochondrial human DNA polymerase (hpol) have been shown to tolerate an entire RNA strand. Y-family hpol is known for translesion synthesis opposite the UV-induced DNA lesion cyclobutane pyrimidine dimer and was recently found to incorporate ribonucleotides into DNA. Here, we report that hpol is able to bind DNA/DNA, RNA/DNA, and DNA/RNA duplexes with similar affinities. In addition, hpol , as well as another Y-family DNA polymerase, hpol , accommodates RNA as one of the two strands during primer extension, mainly by inserting dNMPs opposite unmodified templates or DNA lesions, such as 8-oxo-2-deoxyguanosine or cyclobutane pyrimidine dimer, even in the presence of an equal amount of the DNA/DNA substrate. The discovery of this RNA-accommodating ability of hpol redefines the traditional concept of human DNA polymerases and indicates potential new functions of hpol in vivo.