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Telomere instability initiates and then boosts carcinogenesis by the butterfly effect.
Current Opinion in Genetics & Development ( IF 3.7 ) Pub Date : 2020-04-30 , DOI: 10.1016/j.gde.2020.01.005
Cecile Herate 1 , Laure Sabatier 1
Affiliation  

Telomeres are composed of DNA repeat sequences at the ends of chromosomes that recruit a multitude of proteins to form a complex loop structure at each extremity. The integrity of this structure is critical and correct conformation of the loop is essential for the protection of chromosome ends from DDR signaling. The properties of telomere composition and synthesis result in telomere shortening at each cell division, programming cellular lifespan by driving aged cells towards death. Indeed, many external factors, such as cellular stress, trigger cell-cycle dysfunction and, in some cases, enable the survival of cells with dysfunctionally short telomeres. Destabilized loops at chromosome ends can then lead to dramatic consequences, via a butterfly effect such as multiple chromosomal fusions and rearrangements causing large chromosomal deletions, XXL-LOH (loss of heterozygoty due to very large chromosome deletions, up to whole chromosome arm), the expression of recessive mutations, and potential cell transformation.

中文翻译:

端粒的不稳定性开始并随后通过蝴蝶效应促进癌变。

端粒由染色体末端的DNA重复序列组成,这些序列募集大量蛋白质以在每个末端形成复杂的环结构。该结构的完整性至关重要,并且正确的环构型对于保护染色体末端免受DDR信号传递至关重要。端粒组成和合成的特性导致每个细胞分裂时端粒缩短,通过驱使衰老的细胞死亡来编程细胞寿命。实际上,许多外部因素(例如细胞应激)会触发细胞周期功能障碍,并且在某些情况下,使功能失调的端粒短的细胞得以存活。然后,通过蝴蝶效应(例如多次染色体融合和重排会导致大范围的染色体缺失),染色体末端不稳定的环会导致巨大的后果。
更新日期:2020-03-17
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