CDK-independent role of D-type cyclins in regulating DNA mismatch repair.

Autor:	Rona G; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, NYU Grossman School of Medicine, New York, NY 10016, USA., Miwatani-Minter B; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Zhang Q; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Goldberg HV; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Kerzhnerman MA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Howard JB; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Simoneschi D; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Lane E; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Hobbs JW; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Sassani E; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Wang AA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Keegan S; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA., Laverty DJ; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Piett CG; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Pongor LS; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Cancer Genomics and Epigenetics Core Group, Hungarian Centre of Excellence for Molecular Medicine, Szeged 6728, Hungary., Xu ML; Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02215, USA., Andrade J; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Thomas A; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Sicinski P; Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland., Askenazi M; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Biomedical Hosting LLC, 33 Lewis Avenue, Arlington, MA 02474, USA., Ueberheide B; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA., Fenyö D; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA., Nagel ZD; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Pagano M; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address: michele.pagano@nyulangone.org.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 Apr 04; Vol. 84 (7), pp. 1224-1242.e13. Date of Electronic Publication: 2024 Mar 07.
DOI:	10.1016/j.molcel.2024.02.010
Abstrakt:	Although mismatch repair (MMR) is essential for correcting DNA replication errors, it can also recognize other lesions, such as oxidized bases. In G0 and G1, MMR is kept in check through unknown mechanisms as it is error-prone during these cell cycle phases. We show that in mammalian cells, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins inhibit the proteasomal degradation of p21, which competes with MMR proteins for binding to PCNA, thereby inhibiting MMR. The ability of D-type cyclins to limit MMR is CDK4- and CDK6-independent and is conserved in G0 and G1. At the G1/S transition, the timely, cullin-RING ubiquitin ligase (CRL)-dependent degradation of D-type cyclins and p21 enables MMR activity to efficiently repair DNA replication errors. Persistent expression of D-type cyclins during S-phase inhibits the binding of MMR proteins to PCNA, increases the mutational burden, and promotes microsatellite instability. Competing Interests: Declaration of interests P.S. has been a consultant at Novartis, Genovis, Guidepoint, The Planning Shop, ORIC Pharmaceuticals, Cedilla Therapeutics, Syros Pharmaceuticals, Blueprint Medicines, Curie Bio, Differentiated Therapeutics, Excientia, Blueprint, Ligature Therapeutics, Merck, Redesign Science, Sibylla Biotech, and Exo Therapeutics; his laboratory receives research funding from Novartis. M.P. is or has been an advisor for and has financial interests in SEED Therapeutics, Triana Biomedicines and CullGen, Kymera Therapeutics, and Umbra Therapeutics. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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