Immunological disorders and DNA repair

O'Driscoll, Mark and Jeggo, Penny (2002) Immunological disorders and DNA repair. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 509 (1-2). pp. 109-126. ISSN 0027-5107

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Cellular DNA continuously incurs damage and a range of damage response mechanisms function to maintain genomic integrity in the face of this onslaught. During the development of the immune response, the cell utilises three defined processes, V(D)J recombination, class switch recombination and somatic hypermutation, to create genetic diversity in developing T and B cells. Curiously, the damage response mechanisms employed to maintain genomic stability in somatic cells have been exploited and adapted to help generate diversity during immune development. As a consequence of this overlap, there is mounting evidence that disorders attributable to impaired damage response mechanisms display associated immunodeficiency. Since double strand breaks (DSB) are created during at least two of the mechanisms used to create immunoglobulin diversity, namely V(D)J recombination and class switch recombination, it is not surprising that disorders associated with defects in the response to double strand breaks are those most associated with immunodeficiency. Here, we review the steps involved in the generation of genetic diversity during immune development with a focus on the damage response mechanisms employed and then consider human immunodeficiency disorders associated with impaired damage response mechanisms.

Item Type: Article
Depositing User: Gee Wheatley
Date Deposited: 02 Apr 2007
Last Modified: 10 Sep 2019 14:28
Google Scholar:26 Citations
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