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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >THE BCL2 MAJOR BREAKPOINT REGION IS A SEQUENCE- AND CELL-CYCLE-SPECIFIC BINDING SITE OF THE KU ANTIGEN
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THE BCL2 MAJOR BREAKPOINT REGION IS A SEQUENCE- AND CELL-CYCLE-SPECIFIC BINDING SITE OF THE KU ANTIGEN

机译:BCL2主要突变点区域是KU抗原的序列和细胞周期特异性结合位点

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摘要

The majority of translocations involving BCL2 are very narrowly targeted to three breakpoint clusters evenly spaced over a 100-bp region of the gene's terminal exon. We have recently shown that the immediate upstream boundary of this major breakpoint region (mbr) is a specific recognition site for single-strand DNA (ssDNA) binding proteins on the sense and antisense strands. The downstream flank of the mbr is a helicase binding site. In this report we demonstrate that the helicase and ssDNA binding proteins show reciprocal changes in binding activity over the cell cycle. The helicase is maximally active in G(1) and early S phases; the ssDNA binding proteins are maximally active in late S and G(2)/M phases. An inhibitor of helicase binding appears in late S and G(2)/M. Finally, at least one component of the helicase binding complex is the Ku antigen. Thus, a protein with helicase activity implicated in repair of double-strand breaks, variable (diversity)joining recombination, and, potentially, cell-cycle regulation is targeted to the BCL2 mbr. [References: 33]
机译:涉及BCL2的大多数易位非常狭窄地针对了三个突变点簇,这些簇在基因末端外显子的100 bp区域均匀分布。我们最近显示,这个主要断点区域(mbr)的直接上游边界是有义和反义链上单链DNA(ssDNA)结合蛋白的特异性识别位点。 mbr的下游侧是解旋酶结合位点。在此报告中,我们证明了解旋酶和ssDNA结合蛋白在整个细胞周期内均显示出结合活性的相互变化。解旋酶在G(1)和早期S期中具有最大活性; ssDNA结合蛋白在S和G(2)/ M晚期均具有最大活性。解旋酶结合的抑制剂出现在后期S和G(2)/ M。最后,解旋酶结合复合物的至少一种组分是Ku抗原。因此,具有解旋酶活性的蛋白质涉及双链断裂的修复,可变的(多样性)连接重组以及潜在地细胞周期调节,其靶向于BCL2 mbr。 [参考:33]

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