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Immunological disorders and DNA repair
journal contribution
posted on 2023-06-07, 13:55 authored by Mark O'DriscollMark O'Driscoll, Penny JeggoCellular 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.
History
Publication status
- Published
Journal
Mutation Research - Fundamental and Molecular Mechanisms of MutagenesisISSN
0027-5107Publisher
ElsevierExternal DOI
Issue
1-2Volume
509Page range
109-126Full text available
- No
Peer reviewed?
- Yes