A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats
Mammary tumors are the most prevalent type of tumors in female dogs. Breast cancer 2, early onset (<i>BRCA2</i>) malignant mutations are associated with tumorigenesis in humans and dogs. BRCA2 plays a pivotal role in homologous recombination repair by recruiting RAD51 recombinase to DNA...
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MDPI AG
2023-02-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/10/2/145 |
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| author | Zida Zhu Taisuke Kitano Masami Morimatsu Kazuhiko Ochiai Toshina Ishiguro-Oonuma Kosuke Oosumi Xianghui Lin Koichi Orino Yasunaga Yoshikawa |
| author_facet | Zida Zhu Taisuke Kitano Masami Morimatsu Kazuhiko Ochiai Toshina Ishiguro-Oonuma Kosuke Oosumi Xianghui Lin Koichi Orino Yasunaga Yoshikawa |
| author_sort | Zida Zhu |
| collection | DOAJ |
| description | Mammary tumors are the most prevalent type of tumors in female dogs. Breast cancer 2, early onset (<i>BRCA2</i>) malignant mutations are associated with tumorigenesis in humans and dogs. BRCA2 plays a pivotal role in homologous recombination repair by recruiting RAD51 recombinase to DNA damage sites to maintain genome stability. To recruit RAD51, BRCA2 must interact with RAD51 via BRC repeats, but the regulation of this interaction has been unclear. In this study, we focused on a highly conserved region (HCR) near BRC repeats. Using co-immunoprecipitation and mammalian two-hybrid assay, we found that HCR suppressed the RAD51-interaction activity of BRC repeats and that substitutions of HCR phosphorylation sites affected it. In canine tumor samples, we found ten mutations, including a novel HCR mutation (I1110M) from canine tumor samples. The effect of four HCR mutations, including I1110M, on the RAD51-interaction activity of BRC repeats was tested. One of the HCR mutations found in canine mammary tumors increased the interaction, but the two mutations found in human breast cancers decreased it. This study suggested that the HCR regulated the RAD51-interacting activity of BRC repeats through HCR phosphorylation and that mutations in HCR may be related to tumorigenesis in both dogs and humans. |
| first_indexed | 2024-03-11T08:01:33Z |
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| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-03-11T08:01:33Z |
| publishDate | 2023-02-01 |
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| series | Veterinary Sciences |
| spelling | doaj.art-4c9362d3e1f744d0b3a60d73bb4625c82023-11-16T23:46:15ZengMDPI AGVeterinary Sciences2306-73812023-02-0110214510.3390/vetsci10020145A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC RepeatsZida Zhu0Taisuke Kitano1Masami Morimatsu2Kazuhiko Ochiai3Toshina Ishiguro-Oonuma4Kosuke Oosumi5Xianghui Lin6Koichi Orino7Yasunaga Yoshikawa8Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Towada 034-8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Towada 034-8628, JapanLaboratory of Laboratory Animal Science and Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanLaboratory of Veterinary Hygiene, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo 180-8602, JapanLaboratory of Veterinary Physiology, Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka 020-8550, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Towada 034-8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Towada 034-8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Towada 034-8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Towada 034-8628, JapanMammary tumors are the most prevalent type of tumors in female dogs. Breast cancer 2, early onset (<i>BRCA2</i>) malignant mutations are associated with tumorigenesis in humans and dogs. BRCA2 plays a pivotal role in homologous recombination repair by recruiting RAD51 recombinase to DNA damage sites to maintain genome stability. To recruit RAD51, BRCA2 must interact with RAD51 via BRC repeats, but the regulation of this interaction has been unclear. In this study, we focused on a highly conserved region (HCR) near BRC repeats. Using co-immunoprecipitation and mammalian two-hybrid assay, we found that HCR suppressed the RAD51-interaction activity of BRC repeats and that substitutions of HCR phosphorylation sites affected it. In canine tumor samples, we found ten mutations, including a novel HCR mutation (I1110M) from canine tumor samples. The effect of four HCR mutations, including I1110M, on the RAD51-interaction activity of BRC repeats was tested. One of the HCR mutations found in canine mammary tumors increased the interaction, but the two mutations found in human breast cancers decreased it. This study suggested that the HCR regulated the RAD51-interacting activity of BRC repeats through HCR phosphorylation and that mutations in HCR may be related to tumorigenesis in both dogs and humans.https://www.mdpi.com/2306-7381/10/2/145BRCA2RAD51BRC repeatshighly conserved regioncomparative molecular biologymutation analysis |
| spellingShingle | Zida Zhu Taisuke Kitano Masami Morimatsu Kazuhiko Ochiai Toshina Ishiguro-Oonuma Kosuke Oosumi Xianghui Lin Koichi Orino Yasunaga Yoshikawa A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats Veterinary Sciences BRCA2 RAD51 BRC repeats highly conserved region comparative molecular biology mutation analysis |
| title | A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats |
| title_full | A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats |
| title_fullStr | A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats |
| title_full_unstemmed | A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats |
| title_short | A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats |
| title_sort | highly conserved region in brca2 suppresses the rad51 interaction activity of brc repeats |
| topic | BRCA2 RAD51 BRC repeats highly conserved region comparative molecular biology mutation analysis |
| url | https://www.mdpi.com/2306-7381/10/2/145 |
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