title: Aging impairs double-strand break repair by homologous recombination in Drosophila germ cells.
abstract: Aging is characterized by genome instability, which contributes to cancer formation and cell lethality leading to organismal decline. The high levels of DNA double-strand breaks (DSBs) observed in old cells and premature aging syndromes are likely a primary source of genome instability, but the underlying cause of their formation is still unclear. DSBs might result from higher levels of damage or repair defects emerging with advancing age, but repair pathways in old organisms are still poorly understood. Here, we show that premeiotic germline cells of young and old flies have distinct differences in their ability to repair DSBs by the error-free pathway homologous recombination (HR). Repair of DSBs induced by either ionizing radiation (IR) or the endonuclease I-SceI is markedly defective in older flies. This correlates with a remarkable reduction in HR repair measured with the DR-white DSB repair reporter assay. Strikingly, most of this repair defect is already present at 8 days of age. Finally, HR defects correlate with increased expression of early HR components and increased recruitment of Rad51 to damage in older organisms. Thus, we propose that the defect in the HR pathway for germ cells in older flies occurs following Rad51 recruitment. These data reveal that DSB repair defects arise early in the aging process and suggest that HR deficiencies are a leading cause of genome instability in germ cells of older animals.
authors.affiliation: Molecular and Computational Biology Department, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Delabaere
authors.affiliation: Department of Human Science, Georgetown University Medical Center, Washington, DC, 20057, USA.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Ertl
authors.affiliation: Department of Human Science, Georgetown University Medical Center, Washington, DC, 20057, USA.
authors.forename: Dashiell J
authors.initials: DJ
authors.lastname: Massey
authors.affiliation: Department of Human Science, Georgetown University Medical Center, Washington, DC, 20057, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hofley
authors.affiliation: Department of Human Science, Georgetown University Medical Center, Washington, DC, 20057, USA.
authors.forename: Faraz
authors.initials: F
authors.lastname: Sohail
authors.affiliation: Department of Human Science, Georgetown University Medical Center, Washington, DC, 20057, USA.|College of Public Service & Community Solutions, Arizona State University, Phoenix, AZ, 85004, USA.
authors.forename: Elisa J
authors.initials: EJ
authors.lastname: Bienenstock
authors.affiliation: Molecular and Computational Biology Department, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Sebastian
authors.affiliation: Molecular and Computational Biology Department, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Chiolo
authors.affiliation: Department of Human Science, Georgetown University Medical Center, Washington, DC, 20057, USA.
authors.forename: Jeannine R
authors.initials: JR
authors.lastname: LaRocque
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000502:physiology* / Q000528:radiation effects; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D059765:Homologous Recombination / Q000235:genetics*; D008540:Meiosis / Q000528:radiation effects; D008954:Models, Biological; D051135:Rad51 Recombinase / Q000378:metabolism; D011839:Radiation, Ionizing
chemical_list: D029721:Drosophila Proteins; D051135:Rad51 Recombinase; C495149:spn-A protein, Drosophila
keywords: 
  Drosophila melanogaster
  ; Rad51; aging; double-strand break repair; homologous recombination