APOBEC3 subcellular localization and genomic editing

Thumbnail Image

Persistent link to this item

View Statistics

Journal Title

Journal ISSN

Volume Title


APOBEC3 subcellular localization and genomic editing

Published Date




Thesis or Dissertation


The APOBEC proteins are DNA cytosine deaminases with roles in immunity, including retroviral restriction and antibody maturation. Their activity theoretically makes them a danger to genomic DNA. The subfamily of APOBEC3 genes has expanded to included seven different genes in primates. Based on their subcellular localization, only a subset of these APOBEC3 proteins have access to genomic DNA, and may potentially deaminate genomic DNA. Although the nuclear envelope breaks down during mitosis, I demonstrate that none of the APOBEC3s gain access to genomic DNA during cell division. However, APOBEC3B and other APOBEC3 proteins have access to genomic DNA during interphase. I also show that APOBEC3B is actively imported into the nuclear compartment. In general, APOBEC3 nuclear localization and deaminase activity correlate with ability to affect cell cycle progression, implicating these APOBEC3s in deamination of genomic DNA. In support of these conclusions, I observed cell death, activation of the DNA damage response and DNA mutations after ectopic expression of APOBEC3A and APOBEC3B. Moreover, endogenous APOBEC3B is demonstrably nuclear and active in breast cancer cell lines where it causes genomic deamination and mutations. Endogenous APOBEC3B is highly expressed in more than half of human breast cancers compared to normal breast tissues. In addition, sequences from tumors with higher levels of APOBEC3B have more mutations, and these mutations match APOBEC3B's deamination signature. My thesis work further defines the subcellular localization of the APOBEC3 family and provides the first evidence that APOBEC3B is involved in a human cancer type.


University of Minnesota Ph.D. dissertation. October 2012. Major: Biochemistry, Molecular Bio, and Biophysics. Advisor: Reuben S. Harris. 1 computer file (PDF); ix, 182 pages.

Related to




Series/Report Number

Funding information

Isbn identifier

Doi identifier

Previously Published Citation

Suggested citation

Lackey, Lela Lynn. (2012). APOBEC3 subcellular localization and genomic editing. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/161012.

Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.