Phosphorylation Alters the Properties of Pol η: Implications for Translesion Synthesis.
Phosphorylation Alters the Properties of Pol η: Implications for Translesion Synthesis.
复制标题
DOI：
10.1016/j.isci.2018.07.009
复制
发表时间：
2018-08-31
期刊：
影响因子：
5.8
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Peddu C;Zhang S;Zhao H;Wong A;Lee EYC;Lee MYWT;Zhang Z
There are significant ambiguities regarding how DNA polymerase η is recruited to DNA lesion sites in stressed cells while avoiding normal replication forks in non-stressed cells. Even less is known about the mechanisms responsible for Pol η-induced mutations in cancer genomes. We show that there are two safeguards to prevent Pol η from adventitious participation in normal DNA replication. These include sequestration by a partner protein and low basal activity. Upon cellular UV irradiation, phosphorylation enables Pol η to be released from sequestration by PDIP38 and activates its polymerase function through increased affinity toward monoubiquitinated proliferating cell nuclear antigen (Ub-PCNA). Moreover, the high-affinity binding of phosphorylated Pol η to Ub-PCNA limits its subsequent displacement by Pol δ. Consequently, activated Pol η replicates DNA beyond the lesion site and potentially introduces clusters of mutations due to its low fidelity. This mechanism could account for the prevalence of Pol η signatures in cancer genome. Pol η activation requires both ATR and PKC phosphorylation Phosphorylation directly enhances the affinity of Pol η toward Ub-PCNA PDIP38 sequesters Pol η away from normal replication fork Pol δ is not able to displace phosphorylated Pol η from Ub-PCNA complex Biochemistry; Molecular Biology; Molecular Genetics
登录
查看更多内容
DOI：
10.1083/jcb.201008076
发表时间：
2011-01-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Göhler T;Sabbioneda S;Green CM;Lehmann AR
通讯作者：
Lehmann AR
影响因子：
7.2
作者：
Goodman MF;Woodgate R
通讯作者：
Woodgate R
影响因子：
14.9
作者：
Guilliam TA;Bailey LJ;Brissett NC;Doherty AJ
通讯作者：
Doherty AJ
影响因子：
16
作者：
Choe KN;Moldovan GL
通讯作者：
Moldovan GL
影响因子：
4.5
作者：
Hendel A;Krijger PH;Diamant N;Goren Z;Langerak P;Kim J;Reissner T;Lee KY;Geacintov NE;Carell T;Myung K;Tateishi S;D'Andrea A;Jacobs H;Livneh Z
通讯作者：
Livneh Z