Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2
Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2
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DOI：
10.1093/hmg/ddh193
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发表时间：
2004-09-01
影响因子：
3.5
通讯作者：
Groden, J
中科院分区：
文献类型：
--
作者：
Lillard-Wetherell, K;Machwe, A;Groden, J
除了增加的DNA链交换，缺乏RecQ样BLM解旋酶的细胞的细胞遗传学特征是端粒缔合的趋势。我们还报告了额外的细胞和生物化学证据的作用，BLM端粒的维护。BLM与端粒重复蛋白TRF 2在细胞中共定位并复合，所述细胞采用称为ALT（端粒的交替延长）的端粒延长的重组介导机制。BLM与TRF 2共定位于S期和G（2）/M期晚期活跃合成DNA的病灶中;当认为发生ALT时，共定位在S期和G（2）/M期晚期增加。此外，TRF 1和TRF 2直接与BLM相互作用，并在体外调节BLM解旋活性。TRF 2刺激端粒和非端粒底物的BLM解旋，而TRF 1仅抑制端粒底物的BLM解旋。最后，TRF 2刺激BLM解旋与等摩尔浓度的TRF 1，但不是当TRF 1加入摩尔过量。这些数据表明BLM在重组介导的端粒延长中的功能，并支持TRF 1和TRF 2在端粒处协调调节BLM活性的模型。
In addition to increased DNA-strand exchange, a cytogenetic feature of cells lacking the RecQ-Iike BLM helicase is a tendency for telomeres to associate. We also report additional cellular and biochemical evidence for the role of BLM in telomere maintenance. BLM co-localizes and complexes with the telomere repeat protein TRF2 in cells that employ the recombination-mediated mechanism of telomere lengthening known as ALT (alternative lengthening of telomeres). BLM co-localizes with TRF2 in foci actively synthesizing DNA during late S and G(2)/M; co-localization increases in late S and G(2)/M when ALT is thought to occur. Additionally, TRF1 and TRF2 interact directly with BLM and regulate BLM unwinding activity in vitro. Whereas TRF2 stimulates BLM unwinding of telomeric and non-telomeric substrates, TRF1 inhibits BLM unwinding of telomeric substrates only. Finally, TRF2 stimulates BLM unwinding with equimolar concentrations of TRF1, but not when TRF1 is added in molar excess. These data suggest a function for BLM in recombination-mediated telomere lengthening and support a model for the coordinated regulation of BLM activity at telomeres by TRF1 and TRF2.