Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 23, Pages 8780-8785Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0603313103
Keywords
APOBEC3 protein; mutagenesis; retrotransposon; genome stability; intrinsic immunity
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Funding
- NIAID NIH HHS [AI65301, R01 AI065301] Funding Source: Medline
- NIGMS NIH HHS [5T32GM07544, R01 GM060518, GM60518, GM69985, P20 GM069985, T32 GM007544] Funding Source: Medline
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Long interspersed element (LINE) 1 retrotransposons are major genomic parasites that represent approximate to 17% of the human genome. The LINE-1 ORF2 protein is also responsible for the mobility of Alu elements, which constitute a further approximate to 11% of genomic DNA. Representative members of each element class remain mobile, and deleterious retrotransposition events can induce spontaneous genetic diseases. Here, we demonstrate that APOBEC3A and APOBEC3B, two members of the APOBEC3 family of human innate antiretroviral resistance factors, can enter the nucleus, where LINE-1 and Alu reverse transcription occurs, and specifically inhibit both LINE-1 and Alu retrotransposition. These data suggest that the APOBEC3 protein family may have evolved, at least in part, to defend the integrity of the human genome against endogenous retrotransposons.
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