Aging and sperm signals alter DNA break formation and repair in the C. elegans germline
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Date
2022-11-07
Authors
Toraason, Erik
Adler, Victoria L.
Libuda, Diana E.
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS
Abstract
Female reproductive aging is associated with decreased oocyte quality and fertility. The
nematode Caenorhabditis elegans is a powerful system for understanding the biology of
aging and exhibits age-related reproductive defects that are analogous to those observed in
many mammals, including dysregulation of DNA repair. C. elegans germline function is influenced
simultaneously by both reproductive aging and signals triggered by limited supplies
of sperm, which are depleted over chronological time. To delineate the causes of DNA repair
defects in aged C. elegans germlines, we assessed both DNA double strand break (DSB)
induction and repair during meiotic prophase I progression in aged germlines which were
depleted of self-sperm, mated, or never exposed to sperm. We find that germline DSB
induction is dramatically reduced only in hermaphrodites which have exhausted their endogenous
sperm, suggesting that a signal due specifically to sperm depletion downregulates
DSB formation. We also find that DSB repair is delayed in aged germlines regardless of
whether hermaphrodites had either a reduction in sperm supply or an inability to endogenously
produce sperm. These results demonstrate that in contrast to DSB induction, DSB
repair defects are a feature of C. elegans reproductive aging independent of sperm presence.
Finally, we demonstrate that the E2 ubiquitin-conjugating enzyme variant UEV-2 is
required for efficient DSB repair specifically in young germlines, implicating UEV-2 in the
regulation of DNA repair during reproductive aging. In summary, our study demonstrates
that DNA repair defects are a feature of C. elegans reproductive aging and uncovers parallel
mechanisms regulating efficient DSB formation in the germline.
Description
29 pages
Keywords
Sperm, DNA repair, Caenorhabditis elegans, Oocytes, Aging, Gonads, Eggs, Larvae
Citation
Toraason E, Adler VL, Libuda DE (2022) Aging and sperm signals alter DNA break formation and repair in the C. elegans germline. PLoS Genet 18(11): e1010282. https://doi.org/10.1371/journal. pgen.1010282