Abasic and oxidized ribonucleotides embedded in DNA are processed by human APE1 and not by RNase H2.
Abasic and oxidized ribonucleotides embedded in DNA are processed by human APE1 and not by RNase H2.
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DOI：
10.1093/nar/gkx723
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发表时间：
2017-11-02
影响因子：
14.9
通讯作者：
Tell G
中科院分区：
文献类型：
--
作者：
Malfatti MC;Balachander S;Antoniali G;Koh KD;Saint-Pierre C;Gasparutto D;Chon H;Crouch RJ;Storici F;Tell G
核糖核苷5′-单磷酸（rNMPs）是真核细胞DNA中最常见的非标准核苷酸，每个细胞周期有超过1亿个rNMPs在哺乳动物基因组中短暂结合。人核糖核酸酶（RNase） H2是能够在DNA中切割核糖核酸的主要酶。RNase H2是否可以处理碱性或氧化的rNMPs并入DNA尚不清楚。碱基切除修复（BER）途径主要负责将氧化位点和碱基位点修复为DNA。本研究表明，人类RNase H2不能处理DNA中嵌入的基本rNMP （rAP位点）或核糖8oxoG （r8oxoG）位点。相反，我们发现重组纯化的人无尿嘧啶/无嘧啶核酸内切酶-1 （APE1）和来自人细胞提取物的APE1能有效处理DNA中的rAP位点，并且在r8oxoG底物上具有较弱的核糖核酸内切酶和3 ' -核酸外切酶活性。使用生化分析，我们的结果提供了人类酶能够识别和处理嵌入DNA的碱性和氧化核糖核苷酸的证据。
Ribonucleoside 5′-monophosphates (rNMPs) are the most common non-standard nucleotides found in DNA of eukaryotic cells, with over 100 million rNMPs transiently incorporated in the mammalian genome per cell cycle. Human ribonuclease (RNase) H2 is the principal enzyme able to cleave rNMPs in DNA. Whether RNase H2 may process abasic or oxidized rNMPs incorporated in DNA is unknown. The base excision repair (BER) pathway is mainly responsible for repairing oxidized and abasic sites into DNA. Here we show that human RNase H2 is unable to process an abasic rNMP (rAP site) or a ribose 8oxoG (r8oxoG) site embedded in DNA. On the contrary, we found that recombinant purified human apurinic/apyrimidinic endonuclease-1 (APE1) and APE1 from human cell extracts efficiently process an rAP site in DNA and have weak endoribonuclease and 3′-exonuclease activities on r8oxoG substrate. Using biochemical assays, our results provide evidence of a human enzyme able to recognize and process abasic and oxidized ribonucleotides embedded in DNA.
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影响因子：
14.9
作者：
Chon H;Sparks JL;Rychlik M;Nowotny M;Burgers PM;Crouch RJ;Cerritelli SM
通讯作者：
Cerritelli SM
影响因子：
5.6
作者：
Berquist, Brian R.;McNeill, Daniel R.;Wilson, David M., III
通讯作者：
Wilson, David M., III
影响因子：
14.9
作者：
Bauer NC;Corbett AH;Doetsch PW
通讯作者：
Doetsch PW
影响因子：
16.6
作者：
Crespan E;Furrer A;Rösinger M;Bertoletti F;Mentegari E;Chiapparini G;Imhof R;Ziegler N;Sturla SJ;Hübscher U;van Loon B;Maga G
通讯作者：
Maga G
影响因子：
4.8
作者：
Cilli, Piera;Minoprio, Anna;Mazzei, Filomena
通讯作者：
Mazzei, Filomena