APOBEC1 cytosine deaminase activity on single-stranded DNA is suppressed by replication protein A |
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| Authors: | Lai Wong Frederick S Vizeacoumar Franco J Vizeacoumar Linda Chelico |
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| Institution: | Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada;Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon S7N 5E5, Canada;Cancer Research, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan S7S 0A6, Canada |
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| Abstract: | Many APOBEC cytidine deaminase members are known to induce ‘off-target’ cytidine deaminations in 5′TC motifs in genomic DNA that contribute to cancer evolution. In this report, we characterized APOBEC1, which is a possible cancer related APOBEC since APOBEC1 mRNA is highly expressed in certain types of tumors, such as lung adenocarcinoma. We found a low level of APOBEC1-induced DNA damage, as measured by γH2AX foci, in genomic DNA of a lung cancer cell line that correlated to its inability to compete in vitro with replication protein A (RPA) for ssDNA. This suggests that RPA can act as a defense against off-target deamination for some APOBEC enzymes. Overall, the data support the model that the ability of an APOBEC to compete with RPA can better predict genomic damage than combined analysis of mRNA expression levels in tumors and analysis of mutation signatures. |
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