TRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends.
TRF2 and lamin A/C interact to facilitate the functional organization of chromosome ends.
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DOI：
10.1038/ncomms6467
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发表时间：
2014-11-17
影响因子：
16.6
通讯作者：
Kosak, Steven T.
中科院分区：
文献类型：
--
作者：
Wood, Ashley M.;Danielsen, Jannie M. Rendtlew;Lucas, Catherine A.;Rice, Ellen L.;Scalzo, David;Shimi, Takeshi;Goldman, Robert D.;Smith, Erica D.;Le Beau, Michelle M.;Kosak, Steven T.
端粒保护线性基因组的末端，端粒的逐渐丧失与细胞衰老有关。端粒保护涉及端粒重复序列结合因子2（TRF 2）促进的3′端插入端粒DNA，形成t环。我们目前的证据表明，T环也可以形成在间质端粒序列在TRF 2依赖的方式，形成间质T环（ITL）。我们证明，TRF 2协会与间质端粒序列是稳定的共定位与A型核纤层蛋白（核纤层蛋白A/C）。我们还发现核纤层蛋白A/C与TRF 2相互作用，核纤层蛋白A/C水平降低或LMNA突变导致常染色体显性遗传性早衰症-Hutchinson吉尔福德早衰综合征（HGPS）-导致ITL形成减少和端粒丢失。我们提出，细胞和生物体的衰老是交织在一起的，通过TRF 2和核纤层蛋白A/C之间的相互作用对染色体结构的影响。 端粒（一种保护染色体末端的结构）的缩短与细胞衰老有关。在这里，Wood等人提出的证据表明，端粒结合蛋白TRF 2和核纤层蛋白A/C之间的相互作用促进了间质t环的形成并稳定了端粒。
Telomeres protect the ends of linear genomes, and the gradual loss of telomeres is associated with cellular ageing. Telomere protection involves the insertion of the 3′ overhang facilitated by telomere repeat-binding factor 2 (TRF2) into telomeric DNA, forming t-loops. We present evidence suggesting that t-loops can also form at interstitial telomeric sequences in a TRF2-dependent manner, forming an interstitial t-loop (ITL). We demonstrate that TRF2 association with interstitial telomeric sequences is stabilized by co-localization with A-type lamins (lamin A/C). We also find that lamin A/C interacts with TRF2 and that reduction in levels of lamin A/C or mutations in LMNA that cause an autosomal dominant premature ageing disorder—Hutchinson Gilford Progeria Syndrome (HGPS)—lead to reduced ITL formation and telomere loss. We propose that cellular and organismal ageing are intertwined through the effects of the interaction between TRF2 and lamin A/C on chromosome structure. The shortening of telomeres—a structure that protects chromosome ends—is associated with cellular aging. Here, Wood et al. present evidence that interaction between the telomere-binding protein TRF2 and lamin A/C facilitates the formation of interstitial t-loops and stabilizes telomeres.
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DOI：
10.1038/nrg3454
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.4
作者：
Gonzalez-Suarez, Ignacio;Redwood, Abena B.;Gonzalo, Susana
通讯作者：
Gonzalo, Susana
影响因子：
5.6
作者：
Griffith, J;Bianchi, A;de Lange, T
通讯作者：
de Lange, T
影响因子：
30.8
作者：
Broccoli, D;Smogorzewska, A;deLange, T
通讯作者：
deLange, T
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas