Institut Curie, Centre de recherche, 75005 Paris, France.
Front Biosci (Landmark Ed). 2013 Jan 1;18(1):1-20. doi: 10.2741/4084.
Telomeres are nucleoprotein structures at the ends of linear chromosomes that protect them from being recognized as DNA double stranded breaks. Telomeres shorten with every cell division and in the absence of the checkpoint mechanisms critical telomere shortening leads to chromosome end fusions and genomic instability. Cancer cells achieve immortality by engaging in one of the two known mechanisms for telomere maintenance: elongation by telomerase or through recombination. Recombination based elongation of telomeres, also known as alternative lengthening of telomeres or ALT, is prevalent among cancers of mesenchymal origin. However, the conditions favoring ALT emergence are not known. Here we will discuss possible players in ALT mechanisms, including recruitment of telomeres to recombination centers, alterations of telomere associated proteins and modifications at the level of chromatin that could generate recombination permissive conditions at telomeres.
端粒是线性染色体末端的核蛋白结构，可防止它们被识别为 DNA 双链断裂。随着每个细胞分裂，端粒会缩短，而没有关键的检查点机制，端粒的缩短会导致染色体末端融合和基因组不稳定。癌细胞通过两种已知的端粒维持机制之一实现永生：端粒酶延长或通过重组。端粒的重组延长，也称为端粒的替代性延长或 ALT，在间充质来源的癌症中很常见。然而，促进 ALT 出现的条件尚不清楚。在这里，我们将讨论 ALT 机制中的可能参与者，包括端粒向重组中心的募集、端粒相关蛋白的改变以及染色质水平的修饰，这些都可以在端粒处产生有利于重组的条件。
