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A Newly Assigned Role of CTCF in Cellular Response to Broken DNAs

机译:CTCF在蜂窝响应对破碎的DNA中的新分配角色

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摘要

Best known as a transcriptional factor, CCCTC-binding factor (CTCF) is a highly conserved multifunctional DNA-binding protein with 11 zinc fingers. It functions in diverse genomic processes, including transcriptional activation/repression, insulation, genome imprinting and three-dimensional genome organization. A big surprise has recently emerged with the identification of CTCF engaging in the repair of DNA double-strand breaks (DSBs) and in the maintenance of genome fidelity. This discovery now adds a new dimension to the multifaceted attributes of this protein. CTCF facilitates the most accurate DSB repair via homologous recombination (HR) that occurs through an elaborate pathway, which entails a chain of timely assembly/disassembly of various HR-repair complexes and chromatin modifications and coordinates multistep HR processes to faithfully restore the original DNA sequences of broken DNA sites. Understanding the functional crosstalks between CTCF and other HR factors will illuminate the molecular basis of various human diseases that range from developmental disorders to cancer and arise from impaired repair. Such knowledge will also help understand the molecular mechanisms underlying the diverse functions of CTCF in genome biology. In this review, we discuss the recent advances regarding this newly assigned versatile role of CTCF and the mechanism whereby CTCF functions in DSB repair.
机译:最称为转录因子,CCCTC结合因子(CTCF)是具有11个锌指的高度保守的多功能DNA结合蛋白。它在不同的基因组过程中起作用,包括转录激活/抑制,绝缘,基因组印记和三维基因组组织。最近令人生意的是,鉴定CTCF接合DNA双链休息(DSB)的修复以及维持基因组保真度的CTCF。此发现现在为该蛋白质的多方面属性增加了新的尺寸。 CTCF通过通过精细的途径发生的同源重组(HR)促进最精确的DSB修复,其需要一种及时组装/拆卸各种HR修复复合物和染色质修饰,并坐标,以忠实地恢复原始DNA序列破碎的DNA网站。了解CTCF与其他人力资源因子之间的功能性串扰将照亮各种人类疾病的分子基础,这些疾病的范围从发育障碍到癌症,而且因修复受损而产生。这些知识还将有助于了解基因组生物学中CTCF各种功能的分子机制。在本次审查中,我们讨论了关于CTCF的新分配多功能作用的最新进展以及DSB修复中的CTCF函数的机制。

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