Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate
Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate
复制标题
DOI：
10.1038/s41598-020-57886-y
复制
发表时间：
2020-01-22
影响因子：
4.6
通讯作者：
Caglayan, Melike
中科院分区：
文献类型：
--
作者：
Caglayan, Melike
DNA聚合酶(Polu)主要是将核糖核苷酸插入单核苷酸缝隙的DNA中间体中，连接步骤在非同源末端连接(NHEJ)中非互补DNA末端的连接中起着关键作用，以修复由活性氧引起的双链断裂(DSB)。本文报道了8-氧代-2‘-脱氧鸟苷(8-oxodG)与核糖核苷酸(RATP或rCTP)的多聚插入产物(RATP或rCTP)在体外被有效地连接，并且Mn2+的存在刺激了这一偶联反应。此外，我们的结果表明，polu在8-oxodG的突变旁路过程中起到了介导连接的作用，而在NHEJ修复中间体上预先插入的3‘-非正则碱基对(3’-Ra或3‘-Rc)损害了DNA连接酶I或DNA连接酶IV/XRCC4复合体的末端连接。
DNA polymerase (pol) mu primarily inserts ribonucleotides into a single-nucleotide gapped DNA intermediate, and the ligation step plays a critical role in the joining of noncomplementary DNA ends during nonhomologous end joining (NHEJ) for the repair of double-strand breaks (DSBs) caused by reactive oxygen species. Here, we report that the pol mu insertion products of ribonucleotides (rATP or rCTP), instead of deoxyribonucleotides, opposite 8-oxo-2 ' -deoxyguanosine (8-oxodG) are efficiently ligated and the presence of Mn2+ stimulates this coupled reaction in vitro. Moreover, our results point to a role of pol mu in mediating ligation during the mutagenic bypass of 8-oxodG, while 3 ' -preinserted noncanonical base pairs (3 ' -rA or 3 ' -rC) on NHEJ repair intermediates compromise the end joining by DNA ligase I or the DNA ligase IV/XRCC4 complex.