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Comprehensive Chromosome End Remodeling during Programmed DNA Elimination.

Jianbin Wang1, Giovana M B Veronezi2, Yuanyuan Kang2

  • 1Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA; RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA.

Current Biology : CB
|July 18, 2020
PubMed
Summary

Programmed DNA elimination in Ascaris removes DNA from somatic cells, creating new chromosome ends. Eliminated DNA forms micronuclei, undergoing degradation via autophagy.

Keywords:
AscarisEMHi-CPacBiochromosome end remodelinggenome assemblyhistonesmicronucleimitosisnematodeprogrammed DNA eliminationsubtelomeric breakstelomere healingtomographyultrastructure

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Area of Science:

  • Genetics
  • Cell Biology
  • Developmental Biology

Background:

  • Multicellular organisms typically maintain identical germline and somatic genomes.
  • Programmed DNA elimination reduces the somatic genome, a process observed in nematodes like Ascaris.
  • Previous studies identified DNA loss but lacked precise chromosomal localization information.

Purpose of the Study:

  • To determine the chromosomal locations of DNA elimination events in Ascaris.
  • To elucidate the mechanisms and ultrastructural features of programmed DNA elimination.
  • To understand the fate of eliminated DNA and its impact on chromosome structure.

Main Methods:

  • PacBio long-read sequencing for germline and somatic genome assembly.
  • Chromosome conformation capture (Hi-C) for a complete chromosomal view.
  • Ultrastructural analysis of DNA elimination during mitosis.

Main Results:

  • All 24 Ascaris germline chromosomes undergo end remodeling with breaks in subtelomeric regions.
  • Distal sequences, including telomeres, are lost, and new telomeres are formed in somatic cells.
  • Eliminated DNA is packaged into micronuclei-like structures, which are subsequently degraded through autophagy.
  • Evidence suggests chromosome fusions in the germline, resolved by DNA elimination in somatic cells.

Conclusions:

  • This study provides the first chromosomal-level view of programmed DNA elimination in Ascaris.
  • Novel features of DNA elimination, including de novo telomere healing and autophagosome-mediated degradation, are described.
  • Programmed DNA elimination significantly reshapes the genome and chromosome structure during development.