title: APOBEC3 proteins and genomic stability: the high cost of a good defense.
abstract: The human APOBEC3 family of cytidine deaminases constitutes a cellular intrinsic defense mechanism that is effective against a range of viruses and retro-elements. While it is well established that these enzymes are powerful mutators of viral DNA, the possibility that their activity could threaten the integrity of the host genome has only recently begun to be investigated. Here, we discuss the implications of new evidence suggesting that APOBEC3 proteins can mediate the deamination of cellular DNA. The maintenance of genomic integrity in the face of this potential off-target activity must require high fidelity DNA repair and strict regulation of APOBEC3 gene expression and enzyme activity. Conversely, the ability of specific members of the APOBEC3 family to activate DNA damage signaling pathways might also reflect another way that these proteins contribute to the host immune response.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Narvaiza
authors.forename: Sébastien
authors.initials: S
authors.lastname: Landry
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Weitzman
mesh_terms: D000071478:APOBEC Deaminases; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D003641:Deamination; D042822:Genomic Instability; D006801:Humans; D007113:Immunity, Innate; D015398:Signal Transduction; D051981:Uracil-DNA Glycosidase / Q000378:metabolism
chemical_list: D004247:DNA; D051981:Uracil-DNA Glycosidase; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase