Suppr超能文献

开花的时候到了。

Time to bloom.

作者信息

Tikoo Shweta, Sengupta Sagar

机构信息

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

出版信息

Genome Integr. 2010 Nov 4;1(1):14. doi: 10.1186/2041-9414-1-14.

Abstract

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.

摘要

布卢姆综合征(BS)是一种常染色体隐性疾病,由布卢姆解旋酶(在文献中也称为BLM解旋酶或BLM)突变引起。BS患者易患几乎所有类型的癌症。即使在今天,BS患者在临床上仍通过高频率姐妹染色单体交换所表现出的高重组表型来诊断。BLM作为解旋酶的功能及其在同源重组(HR)调控过程中的作用已得到充分表征。然而,在过去几年中,BLM作为DNA损伤传感器的作用已被揭示。例如,已证明BLM在体外可刺激RAD54的ATP酶和染色质重塑活性。这表明BLM可能会增加识别损伤的传感器蛋白的可及性。多年来积累的证据表明,BLM是最早在损伤部位积累的蛋白质之一。最后,BLM还通过整合上游信号并充当传感器与效应蛋白(其中再次包括BLM自身)之间的桥梁,起到“分子节点”的作用,效应蛋白进而修复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其作为“守护者肿瘤抑制因子”的报道作用。在这篇综述中,阐述了记录BLM上游功能的最新文献,并指出了未来的研究方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5a1/2992038/83ab0ac0fbcf/2041-9414-1-14-1.jpg

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