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Updated: Jul 19, 2026
Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
Age-dependent usage of double-strand-break repair pathways
Christine R Preston1, Carlos Flores, William R Engels
1Genetics Department, University of Wisconsin, Madison, Wisconsin 53706, USA.
Abstract:
A DNA double-strand break (DSB) can be repaired by any of several alternative and competing mechanisms. The repaired sequences often differ from the original depending on which mechanism was used so that the cell's "choice" of repair mechanism can have profound genetic consequences. DSBs can accumulate with age , and human diseases that mimic some of the effects of aging, such as increased susceptibility to cancer, are associated with certain defects in DSB repair . The premeiotic germ cells of Drosophila provide a useful model for exploration of the connection between aging and DNA repair because these cells are subject to mortality and other age-related changes , and their DNA repair process is easily quantified. We used Rr3, a repair reporter system in Drosophila, to show that the relative usage of DSB repair mechanisms can change substantially as an organism ages. Homologous repair increased linearly in the male germline from 14% in young individuals to more than 60% in old ones, whereas two other pathways showed a corresponding decrease. Furthermore, the proportion of longer conversion tracts (>156 bp) also increased nearly 2-fold as the flies aged. These findings are relevant to the more general question of how DNA damage and repair are related to aging.
Insights
DNA double-strand break repair mechanisms shift with age in fruit flies. Homologous repair increases significantly in aging germ cells, impacting genetic stability and aging processes.
Area of Science:
- Genetics
- Molecular Biology
- Aging Research
Background:
- DNA double-strand breaks (DSBs) are critical DNA lesions repaired by multiple pathways.
- The choice of DSB repair mechanism influences genetic outcomes and can be linked to aging and disease.
- Defects in DSB repair are associated with aging phenotypes and increased cancer susceptibility.
Purpose of the Study:
- To investigate how DNA double-strand break repair mechanisms change with organismal age.
- To explore the relationship between aging, DNA repair, and genetic consequences in the germline.
- To utilize the Drosophila male germline as a model for age-related DNA repair studies.
Main Methods:
- Employed the Rr3 repair reporter system in Drosophila melanogaster.
- Quantified the relative usage of different DSB repair pathways in male germ cells across age groups.
- Analyzed the length of conversion tracts resulting from DSB repair.
Main Results:
- Observed a significant age-dependent shift in DSB repair pathway usage.
- Homologous repair increased linearly from 14% in young flies to over 60% in aged flies.
- The proportion of longer conversion tracts (>156 bp) nearly doubled in older individuals.
Conclusions:
- The relative usage of DNA repair mechanisms is dynamic and changes substantially with age.
- Aging impacts the fidelity and mechanisms of DNA double-strand break repair in the germline.
- Findings contribute to understanding the interplay between DNA damage, repair, and the aging process.
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