Telomeres at a glance.
نویسنده
چکیده
The linearity of chromosomes creates two major problems for eukaryotic cells: the end-replication problem and the endprotection problem. The end-replication problem stems from the inherent inability of the replication machinery to fully duplicate linear templates. The endprotection problem refers to the propensity of linear chromosome ends to be recognized as DNA double-strand breaks (DSBs). Both problems are surmounted by telomeres, the specific nucleoprotein complexes that adorn chromosome ends. In 2009, the Nobel Prize was awarded to pioneering researchers in the telomere field in recognition of their seminal findings that set the stage for, so far, three decades of vigorous investigation of telomeres and telomerase. In this article, I review our current knowledge and recent findings regarding the function of telomeres, with a focus on the mammalian system. Specifically, I delineate the structure and composition of the telomere and highlight recent discoveries that have elucidated the molecular mechanisms underlying the solutions to both ‘end problems’. Lastly, I describe the perilous consequences of telomere dysfunction during tumorigenesis. The composition of chromosome ends Features of telomeric DNA The telomeric architecture incorporates three known entities: tandem repeats of DNA sequence, a specific set of binding proteins and a non-coding RNA transcript. In mammals, telomeric DNA consists of TTAGGG repeats and their complementary AATCCC sequences and, in humans, its size ranges between 5 and 15 kb. A key feature of the telomere end in all organisms is a 39 single-stranded G-rich overhang (Makarov et al., 1997; McElligott and Wellinger, 1997). Although, it should also be noted that 59 single-stranded C-rich overhangs have been observed in worms (Raices et al., 2008) and can occur transiently in some human cancer cells (Oganesian and Karlseder, 2011). Mammalian G-rich overhangs are 30-500 nucleotides long (Chai et al., 2005) and are generated by
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ورودعنوان ژورنال:
- Journal of cell science
دوره 125 Pt 18 شماره
صفحات -
تاریخ انتشار 2012