APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer
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 bindin...
| Үндсэн зохиолчид: | , , , , , , |
|---|---|
| Формат: | Journal article |
| Хэл сонгох: | English |
| Хэвлэсэн: |
Springer Nature
2023
|
| _version_ | 1826311630131036160 |
|---|---|
| author | McCann, JL Cristini, A Law, EK Tellier, M Beghè, C Murphy, S Gromak, N |
| author_facet | McCann, JL Cristini, A Law, EK Tellier, M Beghè, C Murphy, S Gromak, N |
| author_sort | McCann, JL |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:12:38Z |
| format | Journal article |
| id | oxford-uuid:66e52a0b-b1e6-40f6-8ab4-81973e22941c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:12:38Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:66e52a0b-b1e6-40f6-8ab4-81973e22941c2023-12-08T10:21:14ZAPOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:66e52a0b-b1e6-40f6-8ab4-81973e22941cEnglishSymplectic ElementsSpringer Nature2023McCann, JLCristini, ALaw, EKTellier, MBeghè, CMurphy, SGromak, NThe 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. |
| spellingShingle | McCann, JL Cristini, A Law, EK Tellier, M Beghè, C Murphy, S Gromak, N APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer |
| title | APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer |
| title_full | APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer |
| title_fullStr | APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer |
| title_full_unstemmed | APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer |
| title_short | APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer |
| title_sort | apobec3b regulates r loops and promotes transcription associated mutagenesis in cancer |
| work_keys_str_mv | AT mccannjl apobec3bregulatesrloopsandpromotestranscriptionassociatedmutagenesisincancer AT cristinia apobec3bregulatesrloopsandpromotestranscriptionassociatedmutagenesisincancer AT lawek apobec3bregulatesrloopsandpromotestranscriptionassociatedmutagenesisincancer AT tellierm apobec3bregulatesrloopsandpromotestranscriptionassociatedmutagenesisincancer AT beghec apobec3bregulatesrloopsandpromotestranscriptionassociatedmutagenesisincancer AT murphys apobec3bregulatesrloopsandpromotestranscriptionassociatedmutagenesisincancer AT gromakn apobec3bregulatesrloopsandpromotestranscriptionassociatedmutagenesisincancer |