Humans have seven APOBEC3 DNA cytosine deaminases. The activity of these enzymes 
allows them to restrict a variety of retroviruses and retrotransposons, but may 
also cause pro-mutagenic genomic uracil lesions. During interphase the APOBEC3 
proteins have different subcellular localizations: cell-wide, cytoplasmic or 
nuclear. This implies that only a subset of APOBEC3s have contact with nuclear 
DNA. However, during mitosis, the nuclear envelope breaks down and cytoplasmic 
proteins may enter what was formerly a privileged zone. To address the 
hypothesis that all APOBEC3 proteins have access to genomic DNA, we analyzed the 
localization of the APOBEC3 proteins during mitosis. We show that APOBEC3A, 
APOBEC3C and APOBEC3H are excluded from condensed chromosomes, but become 
cell-wide during telophase. However, APOBEC3B, APOBEC3D, APOBEC3F and APOBEC3G 
are excluded from chromatin throughout mitosis. After mitosis, APOBEC3B becomes 
nuclear, and APOBEC3D, APOBEC3F and APOBEC3G become cytoplasmic. Both structural 
motifs as well as size may be factors in regulating chromatin exclusion. 
Deaminase activity was not dependent on cell cycle phase. We also analyzed 
APOBEC3-induced cell cycle perturbations as a measure of each enzyme's capacity 
to inflict genomic DNA damage. AID, APOBEC3A and APOBEC3B altered the cell cycle 
profile, and, unexpectedly, APOBEC3D also caused changes. We conclude that 
several APOBEC3 family members have access to the nuclear compartment and can 
impede the cell cycle, most likely through DNA deamination and the ensuing DNA 
damage response. Such genomic damage may contribute to carcinogenesis, as 
demonstrated by AID in B cell cancers and, recently, APOBEC3B in breast cancers.