基因组DNA生物遗传信息的重要载体，维持其稳定性和准确性是一切生命活动的基础。除UV射线等外源性刺激之外，细胞在正常生命代谢活动中会发生内源的程序性DNA损伤，包括起始减数分裂同源重组所需的DNA双链断裂;TET家族蛋白介导的主动去甲基化过程所需的DNA单链断裂;适应性免疫中起始基因重排、高频突变、DNA重组等过程以产生抗体多样性的DNA损伤等。程序性损伤通常受到细胞精密地调控以保证遗传信息的完整。然而，如果这些损伤在修复过程中发生错误，例如DNA双链断裂的一端错误地连接到不同染色体断裂的另一端时会导致易位，则可能促进癌症等疾病的发生和影响疾病治疗效果。

　　与此同时，细胞内也存在着大量内源的非程序性损伤，例如DNA复制过程中产生的碱基错配，核苷酸的氧化、烷化、脱氨基化这些异常修饰等。基因组上大量遍布的短串联重复序列(Short Tandem Repeat, STR)也是一个非常重要的非程序损伤来源。STR由1-6个核苷酸通过重复排列组成。根据重复序列的不同，STR可以在RNA转录和DNA复制等过程中形成G四联体(G-quadruplex)、三链DNA(Triplex DNA)、十字架(cruciform)等二级结构，而这些结构极易引起基因组不稳定。

　　我们将利用已开发的用于检测DNA断裂和修复过程的高通量测序技术，结合生物信息学分析方法及分子生物学等多学科技术手段研究不同类型内源性损伤在肿瘤中的影响，包括(但不限于)以下几个方向：1)神经细胞内的程序性DNA损伤与化疗引起的神经损伤之间的关联。2)短重复序列引起的基因组不稳定对肿瘤发生、进展的影响。

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