该开花了。

Q4 Biochemistry, Genetics and Molecular Biology Genome Integrity Pub Date : 2010-11-04 DOI:10.1186/2041-9414-1-14
Shweta Tikoo, Sagar Sengupta
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引用次数: 35

摘要

Bloom综合征(BS)是由于Bloom解旋酶(在文献中称为BLM解旋酶或BLM)突变引起的常染色体隐性遗传病。BS患者易患几乎所有类型的癌症。即使在今天,BS患者在临床上也通过高比率的姐妹染色单体交换表现出的超重组表型来诊断。BLM作为解旋酶的功能及其在同源重组(homologous recombination, HR)调控中的作用已经得到了很好的研究。然而,在过去的几年里,BLM作为DNA损伤传感器的作用已经被揭示出来。例如,已经证明BLM可以在体外刺激RAD54的atp酶和染色质重塑活性。这表明BLM可能增加了识别病变的传感器蛋白的可及性。多年来,越来越多的证据表明,BLM是最早积聚在病变部位的蛋白质之一。最后,BLM还像一个“分子节点”,通过整合上游信号,充当传感器和效应蛋白(也包括BLM本身)之间的桥梁,进而修复DNA损伤。因此,BLM似乎是一种涉及多种功能的蛋白质,所有这些功能可能共同促成了它作为“看守肿瘤抑制因子”的作用。在这篇综述中,最近的文献记录了上游BLM的功能,并指出了未来的发展方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Time to bloom.

Bloom Syndrome (BS) is an autosomal recessive disorder due to mutation in Bloom helicase (referred in literature either as BLM helicase or BLM). Patients with BS are predisposed to almost all forms of cancer. BS patients are even today diagnosed in the clinics by hyper-recombination phenotype that is manifested by high rates of Sister Chromatid Exchange. The function of BLM as a helicase and its role during the regulation of homologous recombination (HR) is well characterized. However in the last few years the role of BLM as a DNA damage sensor has been revealed. For example, it has been demonstrated that BLM can stimulate the ATPase and chromatin remodeling activities of RAD54 in vitro. This indicates that BLM may increase the accessibility of the sensor proteins that recognize the lesion. Over the years evidence has accumulated that BLM is one of the earliest proteins that accumulates at the site of the lesion. Finally BLM also acts like a "molecular node" by integrating the upstream signals and acting as a bridge between the transducer and effector proteins (which again includes BLM itself), which in turn repair the DNA damage. Hence BLM seems to be a protein involved in multiple functions - all of which may together contribute to its reported role as a "caretaker tumor suppressor". In this review the recent literature documenting the upstream BLM functions has been elucidated and future directions indicated.

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来源期刊
Genome Integrity
Genome Integrity Biochemistry, Genetics and Molecular Biology-Genetics
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