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@article{Periyasamy:2017:nar/gkx721,
author = {Periyasamy, M and Singh, A and Gemma, C and Kranjec, C and Farzan, R and Leach, D and Navaratnam, N and Palinkas, HL and Vertessy, BG and Fenton, TR and Doorbar, J and Fuller-Pace, F and Meek, DW and Coombes, RC and Buluwela, L and Ali, S},
doi = {nar/gkx721},
journal = {Nucleic Acids Research},
pages = {11056--11069},
title = {p53 controls expression of the DNA deaminase APOBEC3B to limit its potential mutagenic activity in cancer cells},
url = {http://dx.doi.org/10.1093/nar/gkx721},
volume = {45},
year = {2017}
}

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TY  - JOUR
AB  - Cancer genome sequencing has implicated the cytosine deaminase activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) genes as an important source of mutations in diverse cancers, with APOBEC3B (A3B) expression especially correlated with such cancer mutations. To better understand the processes directing A3B over-expression in cancer, and possible therapeutic avenues for targeting A3B, we have investigated the regulation of A3B gene expression. Here, we show that A3B expression is inversely related to p53 status in different cancer types and demonstrate that this is due to a direct and pivotal role for p53 in repressing A3B expression. This occurs through the induction of p21 (CDKN1A) and the recruitment of the repressive DREAM complex to the A3B gene promoter, such that loss of p53 through mutation, or human papilloma virus-mediated inhibition, prevents recruitment of the complex, thereby causing elevated A3B expression and cytosine deaminase activity in cancer cells. As p53 is frequently mutated in cancer, our findings provide a mechanism by which p53 loss can promote cancer mutagenesis.
AU  - Periyasamy,M
AU  - Singh,A
AU  - Gemma,C
AU  - Kranjec,C
AU  - Farzan,R
AU  - Leach,D
AU  - Navaratnam,N
AU  - Palinkas,HL
AU  - Vertessy,BG
AU  - Fenton,TR
AU  - Doorbar,J
AU  - Fuller-Pace,F
AU  - Meek,DW
AU  - Coombes,RC
AU  - Buluwela,L
AU  - Ali,S
DO  - nar/gkx721
EP  - 11069
PY  - 2017///
SN  - 1362-4962
SP  - 11056
TI  - p53 controls expression of the DNA deaminase APOBEC3B to limit its potential mutagenic activity in cancer cells
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkx721
UR  - http://hdl.handle.net/10044/1/50376
VL  - 45
ER  -

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