端粒延长替代机制与DNA修复途径

Alternative Lengthening of Telomere and DNA Repair

端粒长度和结构的稳定与肿瘤及衰老的发生密切相关,端粒维持机制(telomere maintenance mechanism,TMM)的激活对稳定基因组和建立细胞永生化至关重要。85%~90%的肿瘤细胞是通过激活端粒酶来维持端粒长度的,10%~15%的肿瘤细胞在端粒酶失活或不足的情况下,利用同源重组或其他多种机制维持端粒长度,这些端粒维持机制统称为端粒延长替代机制(alterative lengthening of telomere,ALT)。ALT端粒DNA通过染色体外游离的端粒重复DNA来合成。这提示,在ALT端粒维持时进行的DNA修复机制可能有利于阐明衰老与肿瘤之间的辩证关系。该文从ALT端粒DNA维持的角度,阐述和总结了ALT肿瘤中几种DNA修复途径及ALT活性相关蛋白如何维持端粒长度和功能的完整性。

The maintenance of telomere length and structure is highly related to the progress of senescence and tumorigenesis. Activation of a telomere maintenance mechanism（TMM） is of crucial importance for genome stability and the establishment of cellular immortality. 85%-90% of the tumor cells reactivate telomerase to maintain telomere length, while 10%-15% of the tumor cells utilize homologous recombination or other mechanisms to main telomere length in the case of telomerase deficiency. These mechanisms are referred to as alternative lengthening of telomere（ALT）. ALT telomere DNA is synthesized by extrachromosomal free telomeric repeat DNA. Which implicated that DNA repair pathways engaged in ALT telomere maintenance might facilitate the understanding of the crosstalk between senescence and tumorigenesis. From the perspective of ALT telomere DNA, we discuss how DNA repair pathways converage in ALT mechanism and the proteins involved in maintaining the length and functional integrity of telomere in ALT cancers.