PRIMPOL ready, set, reprime!
PRIMPOL ready, set, reprime!
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PRIMPOL准备就绪，设置，重新启动！
DOI：
10.1080/10409238.2020.1841089
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发表时间：
2021-03
影响因子：
6.5
通讯作者：
Vindigni A
中科院分区：
文献类型：
--
作者：
Tirman S;Cybulla E;Quinet A;Meroni A;Vindigni A
DNA复制叉不断受到内源性和外源性DNA损伤的挑战。DNA损伤耐受机制通过使用具有通过受损模板复制的能力的专门的DNA聚合酶，或通过跳过受损的DNA，使其在复制后被修复，确保DNA复制在对复制叉延伸的影响最小的情况下继续。这些机制在细菌、酵母和高等真核生物中是进化上保守的，并且对于确保基因组的及时和忠实复制至关重要。引发酶和DNA定向聚合酶（PRIMPOL）是最近发现的一种同时具有引发酶和聚合酶活性的酶。PRIMPOL正在成为DNA损伤耐受性的关键参与者，特别是在脊椎动物和人类细胞中。在这里，我们审查我们目前的理解PRIMPOL在DNA损伤耐受性的功能，通过集中在定义其双重酶活性的结构方面，以及控制其染色质招募和表达水平的机制。我们还关注PRIMPOL的线粒体和核功能的最新发现，以及这些功能丧失对基因组稳定性和细胞存活的影响。确定PRIMPOL在DNA损伤耐受中的功能在人类疾病的背景下变得越来越重要。特别是，我们讨论了最近的证据，指出PRIMPOL途径作为一种新的分子靶点，以改善癌细胞对DNA损伤化疗的反应，并作为一个预测参数，以分层患者在个性化的癌症治疗。
DNA replication forks are constantly challenged by DNA lesions induced by endogenous and exogenous sources. DNA damage tolerance mechanisms ensure that DNA replication continues with minimal effects on replication fork elongation either by using specialized DNA polymerases, which have the ability to replicate through the damaged template, or by skipping the damaged DNA, leaving it to be repaired after replication. These mechanisms are evolutionarily conserved in bacteria, yeast, and higher eukaryotes, and are paramount to ensure timely and faithful duplication of the genome. The Primase and DNA-directed Polymerase (PRIMPOL) is a recently discovered enzyme that possesses both primase and polymerase activities. PRIMPOL is emerging as a key player in DNA damage tolerance, particularly in vertebrate and human cells. Here, we review our current understanding of the function of PRIMPOL in DNA damage tolerance by focusing on the structural aspects that define its dual enzymatic activity, as well as on the mechanisms that control its chromatin recruitment and expression levels. We also focus on the latest findings on the mitochondrial and nuclear functions of PRIMPOL and on the impact of loss of these functions on genome stability and cell survival. Defining the function of PRIMPOL in DNA damage tolerance is becoming increasingly important in the context of human disease. In particular, we discuss recent evidence pointing at the PRIMPOL pathway as a novel molecular target to improve cancer cell response to DNA-damaging chemotherapy and as a predictive parameter to stratify patients in personalized cancer therapy.
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影响因子：
4.5
作者：
Ameur A;Stewart JB;Freyer C;Hagström E;Ingman M;Larsson NG;Gyllensten U
通讯作者：
Gyllensten U
影响因子：
16
作者：
Bianchi, Julie;Rudd, Sean G.;Jozwiakowski, Stanislaw K.;Bailey, Laura J.;Soura, Violetta;Taylor, Elaine;Stevanovic, Irena;Green, Andrew J.;Stracker, Travis H.;Lindsay, Howard D.;Doherty, Aidan J.
通讯作者：
Doherty, Aidan J.
宇宙（癌症中的体细胞突变目录）数据库和网站。
影响因子：
8.8
作者：
Bamford, S;Dawson, E;Forbes, S;Clements, J;Pettett, R;Dogan, A;Flanagan, A;Teague, J;Futreal, PA;Stratton, MR;Wooster, R
通讯作者：
Wooster, R
影响因子：
64.8
作者：
Ray Chaudhuri A;Callen E;Ding X;Gogola E;Duarte AA;Lee JE;Wong N;Lafarga V;Calvo JA;Panzarino NJ;John S;Day A;Crespo AV;Shen B;Starnes LM;de Ruiter JR;Daniel JA;Konstantinopoulos PA;Cortez D;Cantor SB;Fernandez-Capetillo O;Ge K;Jonkers J;Rottenberg S;Sharan SK;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
14.9
作者：
Diamant N;Hendel A;Vered I;Carell T;Reissner T;de Wind N;Geacinov N;Livneh Z
通讯作者：
Livneh Z