Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2
Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2
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DOI：
10.1038/ng1097-231
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发表时间：
1997-10-01
期刊：
影响因子：
30.8
通讯作者：
deLange, T
中科院分区：
文献类型：
--
作者：
Broccoli, D;Smogorzewska, A;deLange, T
人类端粒由TTAGGG重复序列的长阵列组成，所述TTAGGG重复序列形成染色体末端的保护和复制所需的核蛋白复合物。人端粒的一种组分是TTAGGG重复结合因子1（TRF 1），一种普遍表达的蛋白质，与原癌基因Myb相关，在整个细胞周期中存在于端粒（1-6）。最近的证据表明TRF 1参与了端粒长度的控制（7）。TRF 1被认为是端粒酶的抑制剂，顺式作用以限制单个染色体末端的延伸。在这里，我们报告的TRF 2，TRF 1，携带一个非常相似的Myb相关的DNA结合基序的远端同源克隆。与TRF 1一样，TRF 2在体外广泛表达，特异性结合于双链TTAGGG重复序列，并定位于中期染色体中的所有人类端粒。TRF 2具有与TRF 1类似的结构，因为它携带C末端Myb基序和靠近其N末端的大的TRF 1相关的二聚化结构域。然而，TRF 1和TRF 2的二聚化结构域没有相互作用，表明这些蛋白质主要以同源二聚体存在。虽然TRF 2具有相似的端粒结合活性和结构域组织，但TRF 2与TRF 1的不同之处在于其N末端是碱性的而不是酸性的，并且TRF 2比TRF 1保守得多。结果表明，在人类和小鼠染色体末端的TTAGGG重复序列与两种相关蛋白结合。由于TRF 1和TRF 2表现出显着的差异，我们认为，这些因素在端粒有不同的功能。
Human telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex required for the protection and replication of chromosome ends. One component of human telomeres is the TTAGGG repeat binding factor 1 (TRF1), a ubiquitously expressed protein, related to the protooncogene Myb, that is present at telomeres throughout the cell cycle(1-6). Recent evidence has implicated TRF1 in the control of telomere length(7). TRF1 is proposed to be an inhibitor of telomerase, acting in cis to limit the elongation of individual chromosome ends. Here we report the cloning of TRF2, a distant homologue of TRF1 that carries a very similar Myb-related DNA-binding motif. Like TRF1, TRF2 was ubiquitously expressed, bound specifically to duplex TTAGGG repeats in vitro and localized to all human telomeres in metaphase chromosomes. TRF2 was shown to have an architecture similar to that of TRF1 in that it carries a C-terminal Myb motif and a large TRF1-related dimerization domain near its N terminus. However, the dimerization domain of TRF1 and TRF2 did not interact, suggesting that these proteins exist predominantly as homodimers. While having similar telomere binding activity and domain organization, TRF2 differed from TRF1 in that its N terminus was basic rather than acidic, and TRF2 was much more conserved than TRF1. The results indicate that the TTAGGG repeat arrays at the ends of human and mouse chromosomes bind to two related proteins. Because TRF1 and TRF2 showed significant differences, we suggest that these factors have distinct functions at telomeres.