Human DNA polymerase η accommodates RNA for strand extension

被引:29
作者
Su, Yan [1 ]
Egli, Martin [1 ]
Guengerich, F. Peter [1 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Biochem, 638B Robinson Res Bldg,2200 Pierce Ave, Nashville, TN 37232 USA
基金
美国国家卫生研究院;
关键词
DNA damage; DNA enzyme; DNA polymerase; reverse transcription; RNA; DNA enzymes; replication initiation; reverse transcriptase; RIBONUCLEOTIDE INCORPORATION; XERODERMA-PIGMENTOSUM; REVERSE-TRANSCRIPTASE; REPLICATION; MECHANISM; BYPASS; REPAIR; DISCRIMINATION; FIDELITY; BIOLOGY;
D O I
10.1074/jbc.M117.809723
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:18044 / 18051
页数:8
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