DNA interstrand crosslink repair and cancer.
DNA interstrand crosslink repair and cancer.
复制标题
DOI：
10.1038/nrc3088
复制
发表时间：
2011-06-24
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
链间交联（ICL）是一种高毒性的DNA损伤，通过抑制DNA链分离来阻止转录和复制。诱导ICL的药物是最早且仍然是最广泛使用的化疗药物形式之一。然而，直到最近，我们才开始了解细胞如何修复这些病变。重要的见解来自对范可尼贫血（FA）患者的研究，这是一种罕见的遗传性疾病，导致ICL敏感性。了解FA途径如何连接核酸酶、解旋酶和其他DNA加工酶，应该会导致ICL诱导剂在癌症治疗中更有针对性的使用，并可能为耐药性提供新的见解。
Interstrand crosslinks (ICLs) are highly toxic DNA lesions that prevent transcription and replication by inhibiting DNA strand separation. Agents that induce ICLs were one of the earliest, and are still the most widely used, forms of chemotherapeutic drug. Only recently, however, have we begun to understand how cells repair these lesions. Important insights have come from studies of individuals with Fanconi anaemia (FA), a rare genetic disorder that leads to ICL sensitivity. Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance.