Telomere dysfunction, genome instability and cancer

摘要: Telomeres are highly specialized structures at the ends of chromosomes that made up tandem 5'-TTAGGG-3' repeats and a number telomere associated proteins. By forming loop structures, very end is concealed distinguished from DNA break, thus protecting end-to-end fusions, misrepair degradation. Telomere length maintained by an enzyme called telomerase which weak or undetectable in most normal human somatic cells. In telomerase-negative cells, telomeric progressively lost with cell divisions until cells undergo replicative senescence, serves as intrinsic mechanism to prevent replicating indefinitely. checkpoint defective dysfunction resulting excessive attrition disruption structure may initiate chromosomal instability through fusion unprotected chromosomes. Through propagation breakage-fusion-bridge (BFB) cycles, genetic aberrations characteristic cancers, including aneuploidy, loss heterozygosity, gene amplification can be generated. vitro, extensive succumb crisis characterized wide-spread death. It has been reported surviving either have activated telomerase, use alternative lengthening (ALT) stabilize existing telomeres alleviate chromosome instability. The immortalized post-crisis potential acquire additional alterations for malignant transformation. this review, we summarize our knowledge on association between dysfunction, genomic cancer development.