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Review:Mechanisms of inherited cancer susceptibility

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第1期9卷 1-4页

作者： Shirley HODGSON Department of Cancer Genetics St Georges HospitalUniversity of LondonLondon SW17 OREUK

A small proportion of many cancers are due to inherited mutations in genes,which result in a high risk to the indi-vidual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes,onco-genes,genes encoding proteins involved in dna repair and cell cycle control,and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.

关键词：癌症遗传变异 dna修补肿瘤抑制基因致癌基因

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Functional analysis of the sbcD (dr1921) gene of the extremely radioresistant bacterium Deinococcus radiodurans

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Chinese Science Bulletin 2007年第18期52卷 2506-2513页

作者： HU YiHuai MA ChenYu TIAN Bing LIN Jun HUA YueJin Key Laboratory of Chinese Ministry of Agriculture for Nuclear-Agricultural Sciences Institute of Nuclear-Agricultural Sciences Zhejiang University Hangzhou 310029 China College of Life Sciences Zhejiang University Hangzhou 310029 China College of Life Sciences and Chemical Engineering Huaiyin Institute of Technology Huai'an 223001 China

In eukaryotes, the Mre11-Rad50-Nbs1 (MRN) complex, which resides at the crossroads of dna repair and checkpoint signaling, rapidly forms prominent foci at damage sites following double-strand break (DSB) induction. This complex carries out the initial processing of the DSB ends. Mutations in the genes that encode components of this complex result in dna-damage hypersensitivity, genomic in- stability, telomere shortening, and aberrant meiosis. Therefore, the MR proteins are highly conserved during evolution. The bacterial orthologs of Mre11 and Rad50 are the SbcD and SbcC proteins, respec- tively. Deinococcus radiodurans, an extremely radioresistant bacterium, is able to mend hundreds of radiation-induced DSBs. The SbcD and SbcC proteins were identified as the products of the Dr1921 and Dr1922 genes. Disruption of the sbcD gene, by direct reverse-orientation insertional mutagenesis tech- nology, remarkably increases the cells’ sensitivity to various types of dna damaging agents, such as ionizing radiation, ultraviolet irradiation, hydrogen peroxide, and mitomycin C. We also provide evidence that the drSbcD protein plays an important role in both growth and dna repair in this organ- ism, especially in repair of DSBs generated after cellular exposure to 6000 Gy of IR. These results demonstrate that the drSbcD protein plays an important role in DSBs repair in D. radiodurans.

关键词：辐射阻抗细菌基因分析泛函分析 dna修补

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