Alternative lengthening of telomeres: models, mechanisms and implications

被引:733
作者
Cesare, Anthony J. [1 ,2 ,3 ]
Reddel, Roger R. [1 ,2 ]
机构
[1] Childrens Med Res Inst, Canc Res Unit, Sydney, NSW, Australia
[2] Univ Sydney, Sydney, NSW 2006, Australia
[3] Salk Inst Biol Studies, La Jolla, CA 92037 USA
基金
美国国家科学基金会;
关键词
PROMYELOCYTIC LEUKEMIA BODIES; IMMORTAL HUMAN-CELLS; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; EPIGENETIC REGULATION; MAMMALIAN TELOMERES; FLAP ENDONUCLEASE-1; CANCER-CELLS; PML BODIES; ALT CELLS;
D O I
10.1038/nrg2763
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Unlimited cellular proliferation depends on counteracting the telomere attrition that accompanies DNA replication. In human cancers this usually occurs through upregulation of telomerase activity, but in 10-15% of cancers - including some with particularly poor outcome - it is achieved through a mechanism known as alternative lengthening of telomeres (ALT). ALT, which is dependent on homologous recombination, is therefore an important target for cancer therapy. Although dissection of the mechanism or mechanisms of ALT has been challenging, recent advances have led to the identification of several genes that are required for ALT and the elucidation of the biological significance of some phenotypic markers of ALT. This has enabled development of a rapid assay of ALT activity levels and the construction of molecular models of ALT.
引用
收藏
页码:319 / 330
页数:12
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