摘要
聚集的DNA损伤是电离辐射的特征性特征,被定义为在单个辐射径迹通过之后在20个BPS内形成的两个或多个损伤位点。聚集的DNA损伤分为两大类:双链断裂(DSBS)和非DSB簇,也称为氧化诱导的聚集性DNA损伤(OCDLS),其可能涉及两条相反的链或相同的链。随着辐射在癌症治疗和成像技术中获得更广泛的关注,其对遗传毒性的和辐射引起的DNA损伤修复的机制详细认识仍然有待探索。在这篇综述中,我们研究细胞对聚集性DNA损伤的治疗方法,特别是利用5’,8-环-2’-脱氧嘌呤。由于基底切除修复处理孤立病灶,复杂的损伤更难以修复。根据簇内病变的数量,其的类型及相互分布,长补丁BER或NER被激活。在修复相反病变的过程中,可以产生DSBs,这是修复通过非同源末端连接(NHEJ)或同源重组(HR)。单个病灶在簇内的修复将逐渐进行。这种特殊损伤的较慢处理可能导致严重的生物后果,例如错误修复、突变和染色体重排,因为它增强了集群在修复之前遇到复制叉的可信性。此外我们还讨论了聚集性DNA损伤对细胞存活的影响以及它们与放射治疗和放射诊断的疗效和安全性的相关性。
关键词: 聚集性DNA损伤,5’,8-环-2’-脱氧嘌呤,碱基切除修复,电离辐射,放疗,串联病变。
Current Medicinal Chemistry
Title:The Clustered DNA Lesions – Types, Pathways of Repair and Relevance to Human Health
Volume: 25 Issue: 23
关键词: 聚集性DNA损伤,5’,8-环-2’-脱氧嘌呤,碱基切除修复,电离辐射,放疗,串联病变。
摘要: The clustered DNA lesions are a characteristic feature of ionizing radiation and are defined as two or more damage sites formed within 20 bps after the passage of a single radiation track. The clustered DNA lesions are divided into two major groups: double-stranded breaks (DSBs) and non-DSB clusters also known as Oxidatively-induced Clustered DNA Lesions (OCDLs), which could involve either two opposing strands or the same strand. As irradiation is gaining greater interest in cancer treatment as well as in imaging techniques, the detailed knowledge of its genotoxicity and the mechanisms of repair of radiation-induced DNA damage remain issues to explore. In this review we look at the ways the cell copes with clustered DNA lesions, especially with 5′,8-cyclo-2′-deoxypurines. As the base excision repair deals with isolated lesions, complex damage is more difficult to repair. Depending on the number of lesions within a cluster, their types and mutual distribution, long-patch BER or NER are activated. During the repair of opposing lesions, DSBs could be generated, which are repaired either by nonhomologous end joining (NHEJ) or homologous recombination (HR). The repair of individual lesions within a cluster progresses gradually. This slower processing of particular damage might lead to severe biological consequences such as misrepair, mutations and chromosomal rearrengement as it enhances the plausibility of a cluster encountering a replication fork prior to its repair. The consequences of clustered DNA lesions on cell survival and their relevance to the efficacy and safety of radiotherapy and radiodiagnosis will also be discussed.
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The Clustered DNA Lesions – Types, Pathways of Repair and Relevance to Human Health, Current Medicinal Chemistry 2018; 25 (23) . https://dx.doi.org/10.2174/0929867325666180226110502
DOI https://dx.doi.org/10.2174/0929867325666180226110502 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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