1. Genomics and Evolutionary Biology
  2. Human Biology and Medicine
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APOBEC3A deaminates transiently exposed single-strand DNA during LINE-1 retrotransposition

  1. Sandra R Richardson
  2. Iñigo Narvaiza
  3. Randy A Planegger
  4. Matthew D Weitzman
  5. John V Moran Is a corresponding author
  1. University of Michigan Medical School, United States
  2. The Salk Institute for Biological Studies, United States
  3. University of Pennsylvania Perelman School of Medicine and the Children's Hospital of Philadelphia, United States
Research Article
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Cite as: eLife 2014;3:e02008 doi: 10.7554/eLife.02008

Abstract

Long INterspersed Element-1 (LINE-1 or L1) retrotransposition poses a mutagenic threat to human genomes. Human cells have therefore evolved strategies to regulate L1 retrotransposition. The APOBEC3 (A3) gene family consists of seven enzymes that catalyze deamination of cytidine nucleotides to uridine nucleotides (C-to-U) in single-strand DNA substrates. Among these enzymes, APOBEC3A (A3A) is the most potent inhibitor of L1 retrotransposition in cultured cell assays. However, previous characterization of L1 retrotransposition events generated in the presence of A3A did not yield evidence of deamination. Thus, the molecular mechanism by which A3A inhibits L1 retrotransposition has remained enigmatic. Here, we have used in vitro and in vivo assays to demonstrate that A3A can inhibit L1 retrotransposition by deaminating transiently exposed single-strand DNA that arises during the process of L1 integration. These data provide a mechanistic explanation of how the A3A cytidine deaminase protein can inhibit L1 retrotransposition.

Article and author information

Author details

  1. Sandra R Richardson

    1. University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  2. Iñigo Narvaiza

    1. The Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    No competing interests declared.
  3. Randy A Planegger

    1. University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  4. Matthew D Weitzman

    1. University of Pennsylvania Perelman School of Medicine and the Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    No competing interests declared.
  5. John V Moran

    1. University of Michigan Medical School, Ann Arbor, United States
    For correspondence
    1. moranj@umich.edu
    Competing interests
    John V Moran, is an inventor on patent 6,150,160. Kazazian HH, Boeke JD, Moran JV, Dombroski BA: Compositions and methods of use of mammalian retrotransposons.

Reviewing Editor

  1. Anne Ferguson-Smith, Reviewing Editor, University of Cambridge, United Kingdom

Publication history

  1. Received: December 5, 2013
  2. Accepted: April 2, 2014
  3. Accepted Manuscript published: April 24, 2014 (version 1)
  4. Version of Record published: April 29, 2014 (version 2)

Copyright

© 2014, Richardson et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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