The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis.
The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis.
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DOI：
10.1038/ncomms12918
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发表时间：
2016-09-21
影响因子：
16.6
通讯作者：
Harris, Reuben S.
中科院分区：
文献类型：
--
作者：
Starrett, Gabriel J.;Luengas, Elizabeth M.;McCann, Jennifer L.;Ebrahimi, Diako;Temiz, Nuri A.;Love, Robin P.;Feng, Yuqing;Adolph, Madison B.;Chelico, Linda;Law, Emily K.;Carpenter, Michael A.;Harris, Reuben S.
Cytosine mutations within TCA/T motifs are common in cancer. A likely cause is the DNA cytosine deaminase APOBEC3B (A3B). However, A3B-null breast tumours still have this mutational bias. Here we show that APOBEC3H haplotype I (A3H-I) provides a likely solution to this paradox. A3B-null tumours with this mutational bias have at least one copy of A3H-I despite little genetic linkage between these genes. Although deemed inactive previously, A3H-I has robust activity in biochemical and cellular assays, similar to A3H-II after compensation for lower protein expression levels. Gly105 in A3H-I (versus Arg105 in A3H-II) results in lower protein expression levels and increased nuclear localization, providing a mechanism for accessing genomic DNA. A3H-I also associates with clonal TCA/T-biased mutations in lung adenocarcinoma suggesting this enzyme makes broader contributions to cancer mutagenesis. These studies combine to suggest that A3B and A3H-I, together, explain the bulk of ‘APOBEC signature' mutations in cancer. The APOBEC family of enzymes are cytidine deaminases with APOBEC3A and APOBEC3B thought to contribute to DNA damage signatures detected in cancer genomes. Here, the authors demonstrate an unappreciated role for APOBEC3H haplotype I in the generation of DNA damage in breast cancer.
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影响因子：
30.8
作者：
Burns, Michael B.;Temiz, Nuri A.;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
DOI：
10.1186/s13058-014-0498-3
发表时间：
2015-01-21
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Harris RS
通讯作者：
Harris RS
影响因子：
64.5
作者：
Harris, RS;Bishop, KN;Malim, MH
通讯作者：
Malim, MH
影响因子：
4.8
作者：
Kohli, Rahul M.;Maul, Robert W.;Stivers, James T.
通讯作者：
Stivers, James T.
影响因子：
3.8
作者：
Doseth, Berit;Ekre, Cecilie;Kavli, Bodil
通讯作者：
Kavli, Bodil