title: APOBEC3 cytidine deaminases in double-strand DNA break repair and cancer promotion.
abstract: High frequency of cytidine to thymidine conversions was identified in the genome of several types of cancer cells. In breast cancer cells, these mutations are clustered in long DNA regions associated with single-strand DNA (ssDNA), double-strand DNA breaks (DSB), and genomic rearrangements. The observed mutational pattern resembles the deamination signature of cytidine to uridine carried out by members of the APOBEC3 family of cellular deaminases. Consistently, APOBEC3B (A3B) was recently identified as the mutational source in breast cancer cells. A3G is another member of the cytidine deaminases family predominantly expressed in lymphoma cells, where it is involved in mutational DSB repair following ionizing radiation treatments. This activity provides us with a new paradigm for cancer cell survival and tumor promotion and a mechanistic link between ssDNA, DSBs, and clustered mutations. Cancer Res; 73(12); 3494-8. ©2013 AACR.
authors.affiliation: Department of Pathology and the Lautenberg Center for General and Tumor Immunology, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Nowarski
authors.forename: Moshe
authors.initials: M
authors.lastname: Kotler
mesh_terms: D000071478:APOBEC Deaminases; D000071480:APOBEC-3G Deaminase; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D043525:Cytosine Deaminase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015778:Minor Histocompatibility Antigens; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy
chemical_list: D004277:DNA, Single-Stranded; D004791:Enzyme Inhibitors; D015778:Minor Histocompatibility Antigens; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; D000071480:APOBEC-3G Deaminase; C502889:APOBEC3 proteins, human; C495794:APOBEC3B protein, human; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase