DNA Polymerase θ: A Cancer Drug Target with Reverse Transcriptase Activity.

DNA Polymerase θ: A Cancer Drug Target with Reverse Transcriptase Activity.
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DOI:
10.3390/genes12081146
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发表时间:
2021-07-27
期刊:
影响因子:
3.5
通讯作者:
Pomerantz RT
Pomerantz RT
中科院分区:
生物学3区
文献类型:
--
作者:
Chen XS;Pomerantz RT

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聚(ADP-核糖)聚合酶(PARP)抑制剂的开发优先杀死同源重组缺陷的细胞,精准医学的出现引发了人们对识别和表征与 HR 因子合成致死的其他 DNA 修复酶的广泛兴趣。 DNA 聚合酶 theta (Polθ) 是一种经过验证的抗癌药物靶标,它与 HR 因子和其他 DNA 修复蛋白合成致死,并赋予细胞对各种基因毒性癌症疗法的抵抗力。自 2003 年首次被定性为解旋酶-聚合酶融合蛋白以来,Polθ 在微同源介导的末端连接 (MMEJ) 和跨损伤合成 (TLS) 方面的许多令人兴奋和意想不到的活性已被发现。在这里,我们对 Polθ 的 DNA 修复活性及其作为药物靶点的潜力进行了简短回顾,并重点介绍了最近的一份报告,该报告揭示了 Polθ 是哺乳动物细胞中天然存在的逆转录酶 (RT)。
The emergence of precision medicine from the development of Poly (ADP-ribose) polymerase (PARP) inhibitors that preferentially kill cells defective in homologous recombination has sparked wide interest in identifying and characterizing additional DNA repair enzymes that are synthetic lethal with HR factors. DNA polymerase theta (Polθ) is a validated anti-cancer drug target that is synthetic lethal with HR factors and other DNA repair proteins and confers cellular resistance to various genotoxic cancer therapies. Since its initial characterization as a helicase-polymerase fusion protein in 2003, many exciting and unexpected activities of Polθ in microhomology-mediated end-joining (MMEJ) and translesion synthesis (TLS) have been discovered. Here, we provide a short review of Polθ‘s DNA repair activities and its potential as a drug target and highlight a recent report that reveals Polθ as a naturally occurring reverse transcriptase (RT) in mammalian cells.
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