The tail that wags the dog: P12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression

LeeM.Y.W.T.; ZhangS.; LinS.H.S.; WangX.; DarzynkiewiczZ.; ZhangZ.; LeeE.Y.C.

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The tail that wags the dog: P12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression

机译：摇动狗的尾巴：DNA聚合酶δ的最小亚基P12被泛素连接酶降解，以响应DNA损伤并在细胞周期进程中

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DNA polymerase δ (Pol δ) is a key enzyme in eukaryotic DNA replication. Human Pol δ is a heterotetramer whose p12 subunit is degraded in response to DNA damage, leading to the in vivo conversion of Pol δ4 to Pol δ3. Two E3 ubiquitin ligases, RNF8 and CRL4Cdt2, participate in the DNA damage-induced degradation of p12. We discuss how these E3 ligases integrate the formation of Pol δ3 and ubiquitinated PCNA for DNA repair processes. CRL4Cdt2 partially degrades p12 during normal cell cycle progression, thereby generating Pol δ3 during S phase. This novel finding extends the current view of the role of Pol δ3 in DNA repair and leads to the hypothesis that it participates in DNA replication. The coordinated regulation of licensing factors and Pol δ3 by CRL4 Cdt2 now opens new avenues for control of DNA replication. A parallel study of Pol δ4 and Pol δ3 in Okazaki fragment processing provides evidence for a role of Pol δ3 in DNA replication. We discuss several new perspectives of the role of the 2 forms of Pol δ in DNA replication and repair, as well the significance of the integration of p12 regulation in DNA repair and cell cycle progression.

机译：DNA聚合酶δ（Polδ）是真核DNA复制中的关键酶。人Polδ是异源四聚体，其p12亚基响应DNA损伤而降解，从而导致Polδ4体内转化为Polδ3。两种E3泛素连接酶RNF8和CRL4Cdt2参与DNA损伤诱导的p12降解。我们讨论了这些E3连接酶如何整合Polδ3和泛素化PCNA的DNA修复过程。 CRL4Cdt2在正常细胞周期进程中会部分降解p12，从而在S期产生Polδ3。这一新发现扩展了当前对Polδ3在DNA修复中的作用的看法，并得出了其参与DNA复制的假设。 CRL4 Cdt2对许可因子和Polδ3的协调调节现在为控制DNA复制开辟了新途径。对Okazaki片段加工中Polδ4和Polδ3的平行研究提供了Polδ3在DNA复制中的作用的证据。我们讨论了两种形式的Polδ在DNA复制和修复中的作用的几个新观点，以及在DNA修复和细胞周期进程中整合p12调控的意义。

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《Cell cycle》 |2014年第1期|共9页
作者
LeeM.Y.W.T.; ZhangS.; LinS.H.S.; WangX.; DarzynkiewiczZ.; ZhangZ.; LeeE.Y.C.;
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正文语种 eng
中图分类细胞生物学;
关键词
Cell cycle; Cell cycle progression; CRL4Cdt2; DNA damage; DNA polymerase δ; DNA replication; P12 subunit; RNF8;

机译：细胞周期;细胞周期进程;CRL4Cdt2;DNA损伤;DNA聚合酶δ;DNA复制;P12亚基;RNF8;

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1. The tail that wags the dog: P12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression [J] . LeeM.Y.W.T., ZhangS., LinS.H.S., Cell cycle . 2014,第1期

机译：摇动狗的尾巴：DNA聚合酶δ的最小亚基P12被泛素连接酶降解，以响应DNA损伤并在细胞周期进程中
2. THE DNA POLYMERASE ALPHA PRIMASE COMPLEX COUPLES DNA REPLICATION, CELL-CYCLE PROGRESSION AND DNA-DAMAGE RESPONSE [Review] [J] . Foiani M., Plevani P., Lucchini G. Trends in biochemical sciences . 1997,第11期

机译：DNA聚合酶α聚合酶复合物DNA复制，细胞周期进展和DNA损伤反应[综述]
3. Characterization of the effects of cisplatin and carboplatin on cell cycle progression and DNA damage response activation in DNA polymerase eta-deficient human cells. [J] . Cruet Hennequart S, Villalan S, Kaczmarczyk A, Cell cycle . 2009,第18期

机译：表征顺铂和卡铂对DNA聚合酶eta缺陷型人类细胞的细胞周期进程和DNA损伤反应激活的影响。
4. Cell-free incorporation of photo-crosslinkable p-benzoyl-L-phenylalanine into the polymerase subunits α and ε of Escherichia coli DNA polymerase III [C] . Kiyoshi Ozawa, Gottfried Otting, Nicholas E. Dixon Incorporating of the Australian Society for Biochemistry and Molecular Biology Combio . 2009

机译：无细胞掺入光交联的p-苯甲酰基-1-苯丙氨酸进入聚合酶亚基α和ε的大肠杆菌DNA聚合酶III
5. Cellular redundancy of mechanisms facilitating damage-induced degradation of the polymerase delta p12 subunit. [D] . LeRoy, Christine Elizabeth. 2014

机译：细胞的冗余机制促进了聚合酶δp12亚基的损伤诱导降解。
6. Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase δ for degradation in response to DNA damage. [O] . Sufang Zhang, Yajing Zhou, Ali Sarkeshik, 2014

机译：将RNF8鉴定为泛素连接酶可参与靶向DNA聚合酶δ的p12亚基以响应DNA损伤而降解。
7. The tail that wags the dog: p12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression [O] . Marietta Y.W.T. Lee, Sufang Zhang, Szu Hua Lin, 2013

机译：摇滚狗的尾部：P12，DNA聚合酶δ的最小亚基，通过泛素连接酶降解DNA损伤和细胞周期进展期间
8. Poly (ADP-Ribose) Polymerase (PARP) is Essential for Sulfur Mustard- Induced DNA Damage Repair, But Has No Role in DNA Ligase Activation [R] . Bhat, K. R. , Benton, B. J. , Ray, R. 2006

机译：聚（aDp-核糖）聚合酶（paRp）是硫芥子诱导的DNa损伤修复的必要条件，但在DNa连接酶激活中没有作用

The tail that wags the dog: P12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression

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