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DNA双链断裂修复与染色体易位

DNA double-strand break repair and chromosome translocations.

作者信息

Agarwal Sheba, Tafel Agnieszka A, Kanaar Roland

机构信息

Department of Cell Biology and Genetics, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands.

出版信息

DNA Repair (Amst). 2006 Sep 8;5(9-10):1075-81. doi: 10.1016/j.dnarep.2006.05.029. Epub 2006 Jun 23.

Abstract

Translocations are genetic aberrations that occur when a broken fragment of a chromosome is erroneously rejoined to another chromosome. The initial event in the creation of a translocation is the formation of a DNA double-strand break (DSB), which can be induced both under physiological situations, such as during the development of the immune system, or by exogenous DNA damaging agents. Two major repair pathways exist in cells that repair DSBs as they arise, namely homologous recombination, and non-homologous end-joining. In some situations these pathways can function inappropriately and rejoin ends incorrectly to produce genomic rearrangements, including translocations. Translocations have been implicated in cancer because of their ability to activate oncogenes. Due to selection at the level of the DNA, the cell, and the tissue certain forms of cancer are associated with specific translocations that can be used as a tool for diagnosis and prognosis of these cancers.

摘要

易位是一种遗传畸变,当染色体的一个断裂片段错误地重新连接到另一条染色体上时就会发生。易位产生的初始事件是DNA双链断裂(DSB)的形成,这在生理情况下(如免疫系统发育期间)或外源性DNA损伤剂的作用下均可诱导发生。细胞中存在两种主要的修复途径来修复出现的DSB,即同源重组和非同源末端连接。在某些情况下,这些途径可能会异常发挥作用,错误地重新连接末端,从而产生包括易位在内的基因组重排。由于易位激活癌基因的能力,它们与癌症有关。由于在DNA、细胞和组织水平上的选择,某些形式的癌症与特定的易位相关,这些易位可作为这些癌症诊断和预后的工具。

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