Effects of the N terminus of mouse DNA polymerase κ on the bypass of a guanine-benzo[a]pyrenyl adduct
Effects of the N terminus of mouse DNA polymerase κ on the bypass of a guanine-benzo[a]pyrenyl adduct
复制标题
小鼠 DNA 聚合酶 kappa N 末端对鸟嘌呤-苯并[a]芘基加合物旁路的影响
DOI：
10.1093/jb/mvv118
复制
发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Guo, Caixia
中科院分区：
文献类型：
--
作者：
Liu, Yang;Ma, Xiaolu;Guo, Caixia
DNA polymerase kappa (Poli), one of the typical member of the Y-family DNA polymerases, has been demonstrated to bypass the 10S (+)-trans-anti-benzo[a]pyrene diol epoxide-N-2-deoxyguanine adducts (BPDE-dG) efficiently and accurately. A large structural gap between the core and little finger as well as an N-clasp domain are essential to its unique translesion capability. However, whether the extreme N-terminus of Poli is required for its activity is unclear. In this work, we constructed two mouse Poli deletions, which have either a catalytic core (mPol kappa(1-516)) or a core without the first 21-residues (mPol kappa(22-516)), and tested their activities in the replication of normal and BPDE-DNA. These two Poli deletions are nearly as efficient as the full length protein (Pol kappa(1-852)) in normal DNA synthesis. However, steady-state kinetics reveals a significant reduction in efficiency of dCTP incorporation opposite the lesion by Pol kappa(22-516), along with increased frequencies for misinsertion compared with Pol kappa(1-852). The next nucleotide insertion opposite the template C immediately following the BPDE-dG was also examined, and the bypass differences induced by deletions were highlighted in both insertion and extension step. We conclude that the extreme N-terminal part of Poli is required for the processivity and fidelity of Poli during translesion synthesis of BPDE-dG lesions.
