DNA repair and anti-cancer mechanisms in the long-lived bowhead whale.

Autor: Firsanov D; Department of Biology, University of Rochester, Rochester, NY, USA., Zacher M; Department of Biology, University of Rochester, Rochester, NY, USA., Tian X; Department of Biology, University of Rochester, Rochester, NY, USA., Sformo TL; Department of Wildlife Management, North Slope Borough, Utqiaġvik (Barrow), AK 99723, USA., Zhao Y; Department of Biology, University of Rochester, Rochester, NY, USA., Tombline G; Department of Biology, University of Rochester, Rochester, NY, USA., Lu JY; Department of Biology, University of Rochester, Rochester, NY, USA., Zheng Z; Department of Biology, University of Rochester, Rochester, NY, USA., Perelli L; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gurreri E; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang L; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Guo J; Department of Biology, University of Rochester, Rochester, NY, USA., Korotkov A; Department of Biology, University of Rochester, Rochester, NY, USA., Volobaev V; Department of Biology, University of Rochester, Rochester, NY, USA., Biashad SA; Department of Biology, University of Rochester, Rochester, NY, USA., Zhang Z; Department of Biology, University of Rochester, Rochester, NY, USA., Heid J; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Maslov A; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Sun S; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Wu Z; Department of Biology, University of Rochester, Rochester, NY, USA., Gigas J; Department of Biology, University of Rochester, Rochester, NY, USA., Hillpot E; Department of Biology, University of Rochester, Rochester, NY, USA., Martinez J; Department of Biology, University of Rochester, Rochester, NY, USA., Lee M; Department of Biology, University of Rochester, Rochester, NY, USA., Williams A; Department of Biology, University of Rochester, Rochester, NY, USA., Gilman A; Department of Biology, University of Rochester, Rochester, NY, USA., Hamilton N; Department of Biology, University of Rochester, Rochester, NY, USA., Haseljic E; Department of Biology, University of Rochester, Rochester, NY, USA., Patel A; Department of Biology, University of Rochester, Rochester, NY, USA., Straight M; Department of Biology, University of Rochester, Rochester, NY, USA., Miller N; Department of Biology, University of Rochester, Rochester, NY, USA., Ablaeva J; Department of Biology, University of Rochester, Rochester, NY, USA., Tam LM; Department of Biology, University of Rochester, Rochester, NY, USA., Couderc C; Department of Biology, University of Rochester, Rochester, NY, USA., Hoopman M; Institute for Systems Biology, Seattle, WA USA., Moritz R; Institute for Systems Biology, Seattle, WA USA., Fujii S; Cancer Research Center of Marseille, Department of Genome Integrity, CNRS UMR7258, Inserm U1068, Institut Paoli-Calmettes, Aix Marseille Univ, Marseille, France., Hayman DJ; School of Biosciences, University of Sheffield, UK., Liu H; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.; Cross-Disciplinary Graduate Program in Biomedical Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA., Cai Y; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA., Leung AKL; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.; McKusick-Nathans Institute of the Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Simons MJP; School of Biosciences, University of Sheffield, UK., Zhang Z; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Nelson CB; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Abegglen LM; Department of Pediatrics & Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.; Peel Therapeutics, Inc., Salt Lake City, UT, USA., Schiffman JD; Department of Pediatrics & Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.; Peel Therapeutics, Inc., Salt Lake City, UT, USA., Gladyshev VN; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Modesti M; Cancer Research Center of Marseille, Department of Genome Integrity, CNRS UMR7258, Inserm U1068, Institut Paoli-Calmettes, Aix Marseille Univ, Marseille, France., Genovese G; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Vijg J; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Seluanov A; Department of Biology, University of Rochester, Rochester, NY, USA.; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA., Gorbunova V; Department of Biology, University of Rochester, Rochester, NY, USA.; Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Nov 05. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1101/2023.05.07.539748
Abstrakt: At over 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth, reaching over 80,000 kg 1 . Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto's Paradox 2 . This phenomenon has been explained by the evolution of additional tumor suppressor genes in other larger animals, supported by research on elephants demonstrating expansion of the p53 gene 3-5 . Here we show that bowhead whale fibroblasts undergo oncogenic transformation after disruption of fewer tumor suppressors than required for human fibroblasts. However, analysis of DNA repair revealed that bowhead cells repair double strand breaks (DSBs) and mismatches with uniquely high efficiency and accuracy compared to other mammals. The protein CIRBP, implicated in protection from genotoxic stress, was present in very high abundance in the bowhead whale relative to other mammals. We show that CIRBP and its downstream protein RPA2, also present at high levels in bowhead cells, increase the efficiency and fidelity of DNA repair in human cells. These results indicate that rather than possessing additional tumor suppressor genes as barriers to oncogenesis, the bowhead whale relies on more accurate and efficient DNA repair to preserve genome integrity. This strategy which does not eliminate damaged cells but repairs them may be critical for the long and cancer-free lifespan of the bowhead whale.
Competing Interests: Competing interests The authors declare no competing interests.
Databáze: MEDLINE
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