The only other known replication problem posed by telomeres was solved in 1985 when it was shown that the enzyme telomerase elongates telomeres, which shorten during every cell division. The second problem posed by telomeres, the so-called end-protection problem, was solved by de Lange and her colleagues when they found that shelterin protects the ends of linear chromosomes, which look like damaged DNA, from unnecessary repair. Working with TRF1, the very first shelterin protein ever to be identified, de Lange and Sfeir have not only unveiled a completely unanticipated replication problem at telomeres, they have also shown how it is solved.

The research lays new groundwork for the study of common fragile sites throughout the genome, explains de Lange. Fragile sites have always been hard to study because no specific DNA sequence preceeds or follows them, she says. In constrast, telomeres represent fragile sites with a known sequence, which may help us understand how common fragile sites break throughout the genome ” and why.

Cell 138(1): 90 ”103 (July 10, 2009) Mammalian Telomeres Resemble Fragile Sites and Require TRF1 for Efficient Replication Agnel Sfeir, Settapong T. Kosiyatrakul, Dirk Hockemeyer, Sheila L. MacRae, Jan Karlseder, Carl L. Schildkraut and Titia de Lange

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