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End resection and telomere healing of DNA double-strand breaks during nematode programmed DNA elimination.

Brandon Estrem | Richard E Davis | Jianbin Wang
Nucleic acids research | 2024

Most DNA double-strand breaks (DSBs) are harmful to genome integrity. However, some forms of DSBs are essential to biological processes, such as meiotic recombination and V(D)J recombination. DSBs are also required for programmed DNA elimination (PDE) in ciliates and nematodes. In nematodes, the DSBs are healed with telomere addition. While telomere addition sites have been well characterized, little is known regarding the DSBs that fragment nematode chromosomes. Here, we used embryos from the human and pig parasitic nematode Ascaris to characterize the DSBs. Using END-seq, we demonstrate that DSBs are introduced before mitosis, followed by extensive end resection. The resection profile is unique for each break site, and the resection generates 3'-overhangs before the addition of neotelomeres. Interestingly, telomere healing occurs much more frequently on retained DSB ends than on eliminated ends. This biased repair of the DSB ends may be due to the sequestration of the eliminated DNA into micronuclei, preventing neotelomere formation at their ends. Additional DNA breaks occur within the eliminated DNA in both Ascaris and Parascaris, ensuring chromosomal breakage and providing a fail-safe mechanism for PDE. Overall, our data indicate that telomere healing of DSBs is specific to the break sites responsible for nematode PDE.

Pubmed ID: 38953168

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NIH HHS, United States
    Id: AI155588
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM151551
  • Agency: University of Tennessee, Knoxville,
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI155588
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI114054
  • Agency: NIH HHS, United States
    Id: AI155588

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