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Permanent link (DOI): https://doi.org/10.7939/R3JC44

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Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair Open Access

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Author or creator
Joyce, E.F.
Pedersen, M.
Tiong, S.
White-Brown, S.K.
Paul, A.
Campbell, S.D.
McKim, K.S.
Additional contributors
Subject/Keyword
oogenesis
checkpoints
recombination
meiosis
double-strand breaks
radiation
Histone H2AX
crossover formations
encodes
telomere maintenance
Type of item
Journal Article (Published)
Language
English
Place
Time
Description
Ataxia telangiectasia–mutated (ATM) and ataxia telangiectasia–related (ATR) kinases are conserved regulators of cellular responses to double strand breaks (DSBs). During meiosis, however, the functions of these kinases in DSB repair and the deoxyribonucleic acid (DNA) damage checkpoint are unclear. In this paper, we show that ATM and ATR have unique roles in the repair of meiotic DSBs in Drosophila melanogaster. ATR mutant analysis indicated that it is required for checkpoint activity, whereas ATM may not be. Both kinases phosphorylate H2AV (γ-H2AV), and, using this as a reporter for ATM/ATR activity, we found that the DSB repair response is surprisingly dynamic at the site of DNA damage. γ-H2AV is continuously exchanged, requiring new phosphorylation at the break site until repair is completed. However, most surprising is that the number of γ-H2AV foci is dramatically increased in the absence of ATM, but not ATR, suggesting that the number of DSBs is increased. Thus, we conclude that ATM is primarily required for the meiotic DSB repair response, which includes functions in DNA damage repair and negative feedback control over the level of programmed DSBs during meiosis.
Date created
2011
DOI
doi:10.7939/R3JC44
License information
Rights
© 2011 Joyce et al. This article is © 2011 Joyce et al. This article is distributed under the terms of a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Citation for previous publication
Joyce, E. F., Pedersen, M., Tiong, S., White-Brown, S. K., Paul, A., Campbell, S. D., & McKim, K. S. (2011). Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair. The Journal of Cell Biology, 195(3), 359-67.
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