The excision of mutagenic DNA adducts by the nucleotide excision repair (NER) pathway is essential for genome stability, which is key to avoiding genetic diseases, premature aging, cancer and neurologic disorders. Due to the need to process an extraordinarily high damage density embedded in the nucleosome landscape of chromatin, NER activity provides a unique functional caliper to understand how histone modifiers modulate DNA damage responses. At least three distinct lysine methyltransferases (KMTs) targeting histones have been shown to facilitate the detection of ultraviolet (UV) light-induced DNA lesions in the difficult to access DNA wrapped around histones in nucleosomes. By methylating core histones, these KMTs generate docking sites for DNA damage recognition factors before the chromatin structure is ultimately relaxed and the offending lesions are effectively excised. In view of their function in priming nucleosomes for DNA repair, mutations of genes coding for these KMTs are expected to cause the accumulation of DNA damage promoting cancer and other chronic diseases. Research on the question of how KMTs modulate DNA repair might pave the way to the development of pharmacologic agents for novel therapeutic strategies.

中文翻译：

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用于DNA损伤识别的染色质支架：组蛋白甲基转移酶如何引发核小体修复紫外线诱导的损伤。

通过核苷酸切除修复（NER）途径切除诱变的DNA加合物对于基因组稳定性至关重要，这对于避免遗传疾病，过早衰老，癌症和神经系统疾病至关重要。由于需要处理嵌入染色质核小体中的异常高的损伤密度，因此NER活性提供了独特的功能卡尺，以了解组蛋白修饰剂如何调节DNA损伤反应。已经证明，靶向组蛋白的至少三种不同的赖氨酸甲基转移酶（KMT）有助于在难以接近包裹在核小体中的组蛋白周围的DNA中检测紫外线（UV）诱导的DNA损伤。通过甲基化核心组蛋白，这些KMT在染色质结构最终被放松并有效切除病变之前就产生了DNA损伤识别因子的停靠位点。考虑到它们在启动核小体修复DNA中的功能，编码这些KMT的基因突变有望引起DNA损伤的积累，从而促进癌症和其他慢性疾病。关于KMT如何调节DNA修复的问题的研究可能为开发新的治疗策略的药理学铺平道路。