IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12918.html
   My bibliography  Save this article

The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis

Author

Listed:
  • Gabriel J. Starrett

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Institute for Molecular Virology, University of Minnesota
    Center for Genome Engineering, University of Minnesota)

  • Elizabeth M. Luengas

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Institute for Molecular Virology, University of Minnesota
    Center for Genome Engineering, University of Minnesota)

  • Jennifer L. McCann

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Institute for Molecular Virology, University of Minnesota
    Center for Genome Engineering, University of Minnesota)

  • Diako Ebrahimi

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Institute for Molecular Virology, University of Minnesota
    Center for Genome Engineering, University of Minnesota)

  • Nuri A. Temiz

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota)

  • Robin P. Love

    (University of Saskatchewan)

  • Yuqing Feng

    (University of Saskatchewan)

  • Madison B. Adolph

    (University of Saskatchewan)

  • Linda Chelico

    (University of Saskatchewan)

  • Emily K. Law

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Institute for Molecular Virology, University of Minnesota
    Center for Genome Engineering, University of Minnesota)

  • Michael A. Carpenter

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Institute for Molecular Virology, University of Minnesota
    Center for Genome Engineering, University of Minnesota)

  • Reuben S Harris

    (Molecular Biology and Biophysics, University of Minnesota
    Masonic Cancer Center, University of Minnesota
    Institute for Molecular Virology, University of Minnesota
    Center for Genome Engineering, University of Minnesota)

Abstract

Cytosine mutations within TCA/T motifs are common in cancer. A likely cause is the DNA cytosine deaminase APOBEC3B (A3B). However, A3B-null breast tumours still have this mutational bias. Here we show that APOBEC3H haplotype I (A3H-I) provides a likely solution to this paradox. A3B-null tumours with this mutational bias have at least one copy of A3H-I despite little genetic linkage between these genes. Although deemed inactive previously, A3H-I has robust activity in biochemical and cellular assays, similar to A3H-II after compensation for lower protein expression levels. Gly105 in A3H-I (versus Arg105 in A3H-II) results in lower protein expression levels and increased nuclear localization, providing a mechanism for accessing genomic DNA. A3H-I also associates with clonal TCA/T-biased mutations in lung adenocarcinoma suggesting this enzyme makes broader contributions to cancer mutagenesis. These studies combine to suggest that A3B and A3H-I, together, explain the bulk of ‘APOBEC signature’ mutations in cancer.

Suggested Citation

  • Gabriel J. Starrett & Elizabeth M. Luengas & Jennifer L. McCann & Diako Ebrahimi & Nuri A. Temiz & Robin P. Love & Yuqing Feng & Madison B. Adolph & Linda Chelico & Emily K. Law & Michael A. Carpenter, 2016. "The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12918
    DOI: 10.1038/ncomms12918
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12918
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12918?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Atanu Maiti & Adam K. Hedger & Wazo Myint & Vanivilasini Balachandran & Jonathan K. Watts & Celia A. Schiffer & Hiroshi Matsuo, 2022. "Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12918. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.