Mignon-Ravix Cécile, Depetris Danielle, Delobel Bruno, Croquette Marie-Françoise, Mattei Marie-Geneviève
INSERM 491, Faculté de Médecine Timone, Marseille, France.
Eur J Hum Genet. 2002 Feb;10(2):107-12. doi: 10.1038/sj.ejhg.5200775.
Mammalian telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex which protects the chromosome ends. Human telomere function is known to require two TTAGGG repeat factors, TRF1 and TRF2, and several interacting proteins, but the mechanism by which the DNA/protein complex prevents end to end fusion in vivo has not been elucidated. In order to better understand the role of specific telomere-associated proteins in the organisation of chromosome ends, we have studied a patient with a rare chromosome rearrangement that has given rise to an interstitial telomere. Using specific antibodies and immuno-FISH on unfixed metaphase chromosomes, we show that the proteins TRF2 and TIN2 (TIN2 interacts with TRF1) co-localise with the interstitial TTAGGG repeats. Our results demonstrate, for the first time in humans, that TRF2 and TIN2 proteins associate with interstitial duplex TTAGGG repeats, in vivo. They confirm that double stranded-telomeric repeats, even when complexed with specific proteins, are not sufficient to create a functional telomere. Finally, they suggest a possible role for proteins in stabilising interstitial TTAGGG repeats.
哺乳动物的端粒由长串的TTAGGG重复序列组成，这些重复序列形成一种核蛋白复合体，保护染色体末端。已知人类端粒功能需要两个TTAGGG重复序列因子，即TRF1和TRF2，以及几种相互作用的蛋白质，但DNA/蛋白质复合体在体内防止染色体末端融合的机制尚未阐明。为了更好地理解特定端粒相关蛋白在染色体末端组织中的作用，我们研究了一名患有罕见染色体重排的患者，该重排产生了一个中间端粒。通过对未固定的中期染色体使用特异性抗体和免疫荧光原位杂交技术，我们发现TRF2和TIN2蛋白（TIN2与TRF1相互作用）与中间的TTAGGG重复序列共定位。我们的结果首次在人类中证明，TRF2和TIN2蛋白在体内与中间双链TTAGGG重复序列相关联。这些结果证实，即使与特定蛋白质复合，双链端粒重复序列也不足以形成功能性端粒。最后，这些结果表明蛋白质在稳定中间TTAGGG重复序列方面可能发挥作用。
