Journal article
APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer
- Abstract:
- The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors. Biochemical experiments show APOBEC3B binding to R-loops in cells and in vitro. Genetic experiments demonstrate R-loop increases in cells lacking APOBEC3B and decreases in cells overexpressing APOBEC3B. Genome-wide analyses show major changes in the overall landscape of physiological and stimulus-induced R-loops with thousands of differentially altered regions, as well as binding of APOBEC3B to many of these sites. APOBEC3 mutagenesis impacts genes overexpressed in tumors and splice factor mutant tumors preferentially, and APOBEC3-attributed kataegis are enriched in RTCW motifs consistent with APOBEC3B deamination. Taken together with the fact that APOBEC3B binds single-stranded DNA and RNA and preferentially deaminates DNA, these results support a mechanism in which APOBEC3B regulates R-loops and contributes to R-loop mutagenesis in cancer.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 14.2MB, Terms of use)
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- Publisher copy:
- 10.1038/s41588-023-01504-w
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Genetics More from this journal
- Volume:
- 55
- Issue:
- 10
- Pages:
- 1721–1734
- Publication date:
- 2023-09-21
- Acceptance date:
- 2023-08-17
- DOI:
- EISSN:
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1546-1718
- ISSN:
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1061-4036
- Language:
-
English
- Keywords:
- Pubs id:
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1522706
- Local pid:
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pubs:1522706
- Deposit date:
-
2023-09-08
- ARK identifier:
Terms of use
- Copyright holder:
- McCann et al
- Copyright date:
- 2023
- Rights statement:
- © 2023 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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