The impact of developmental stage, tissue type, and sex on DNA double-strand break repair in Drosophila melanogaster.

Autor: Graham EL; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, District of Columbia, United States of America., Fernandez J; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, District of Columbia, United States of America., Gandhi S; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, District of Columbia, United States of America., Choudhry I; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, District of Columbia, United States of America., Kellam N; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, District of Columbia, United States of America., LaRocque JR; Department of Human Science, School of Health, Georgetown University Medical Center, Washington, District of Columbia, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2024 Apr 29; Vol. 20 (4), pp. e1011250. Date of Electronic Publication: 2024 Apr 29 (Print Publication: 2024).
DOI: 10.1371/journal.pgen.1011250
Abstrakt: Accurate repair of DNA double-strand breaks (DSBs) is essential for the maintenance of genome integrity, as failure to repair DSBs can result in cell death. The cell has evolved two main mechanisms for DSB repair: non-homologous end-joining (NHEJ) and homology-directed repair (HDR), which includes single-strand annealing (SSA) and homologous recombination (HR). While certain factors like age and state of the chromatin are known to influence DSB repair pathway choice, the roles of developmental stage, tissue type, and sex have yet to be elucidated in multicellular organisms. To examine the influence of these factors, DSB repair in various embryonic developmental stages, larva, and adult tissues in Drosophila melanogaster was analyzed through molecular analysis of the DR-white assay using Tracking across Indels by DEcomposition (TIDE). The proportion of HR repair was highest in tissues that maintain the canonical (G1/S/G2/M) cell cycle and suppressed in both terminally differentiated and polyploid tissues. To determine the impact of sex on repair pathway choice, repair in different tissues in both males and females was analyzed. When molecularly examining tissues containing mostly somatic cells, males and females demonstrated similar proportions of HR and NHEJ. However, when DSB repair was analyzed in male and female premeiotic germline cells utilizing phenotypic analysis of the DR-white assay, there was a significant decrease in HR in females compared to males. This study describes the impact of development, tissue-specific cycling profile, and, in some cases, sex on DSB repair outcomes, underscoring the complexity of repair in multicellular organisms.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Graham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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