ArticleMolecular cell2024
CDK-independent role of D-type cyclins in regulating DNA mismatch repair.
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Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Cyclin D-CDK4/6 couple proliferation to membrane and mitochondrial protein supply through a DeSI1 phospho-switch.bioRxiv : the preprint server for biology · 2026Article
- Targeting casein kinase 1α-mediated FADD phosphorylation restores sensitivity in select CDK4/6 inhibitor-resistant breast cancer models.The Journal of clinical investigation · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Replication associated nuclear DNA mismatch repair across kingdoms.Biochemical Society transactions · 2026Review
- Phosphoproteomic profiling reveals post-translational dysregulation in Huntington's disease patient-derived neurons.Cellular & molecular biology letters · 2026Article
- Deficiency of the mCellular and molecular life sciences : CMLS · 2026Article
- Stabilization of cyclin D3 protein by CDKN1A (p21Cell communication and signaling : CCS · 2026Article
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- Mbd4 and MutSα protect cells from spontaneous deamination of 5-methylcytosine.Nucleic acids research · 2026Article
- p16 expression confers sensitivity to CDK2 inhibitors in cyclin E1-driven ovarian cancers.Science signaling · 2025Article
- Molecular and genetic evidence for the role of AMBRA1 in suppressing S-phase entry and tumorigenesis.iScience · 2025Article
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- The role of ubiquitination in health and disease.MedComm · 2024Review
- Regulation of biological processes by ubiquitin ligases: a focus on the Pagano Lab's contribution.Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
24 authors at 8 institutions in 2 countries.
Gergely RonaDepartment 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.
Bearach Miwatani-MinterDepartment 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.
Qingyue ZhangDepartment 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.
Hailey V GoldbergDepartment 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.
Marc A KerzhnermanDepartment 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.
Jesse B HowardDepartment 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.
Daniele SimoneschiDepartment 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.
Ethan LaneDepartment 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.
John W HobbsDepartment 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.
Elizabeth SassaniDepartment 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.
Andrew A WangDepartment 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.
Sarah KeeganDepartment 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.
Daniel J LavertyHarvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Cortt G PiettHarvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Lorinc S PongorDevelopmental 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.
Miranda Li XuDepartment of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02215, USA.
Joshua AndradeDepartment 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.
Anish ThomasDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Piotr SicinskiDepartment 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.
Manor AskenaziDepartment 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.
Beatrix UeberheideDepartment 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.
David FenyöDepartment 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.
Zachary D NagelHarvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Michele PaganoDepartment 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.
New York University · USNYU Langone’s Laura and Isaac Perlmutter Cancer CenterHarvard University · USDana-Farber Cancer Institute · USCenter for Cancer Research · USHoward Hughes Medical Institute · USInstitute for Systems Biology · USNational Cancer Institute · US
Funding
Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6MTissue and Pathology CoreP50CA168504 · NCI · DANA-FARBER CANCER INST · PI LEIF W ELLISEN, NANCY U LIN · 2013 to 2026
$30.1MExploiting DNA Replicative Stress for Novel Small Cell Lung Cancer TherapiesZIABC011793 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI THOMAS, ANISH · 2018 to 2025
$16.4MTissue and Pathology CoreP01CA250959 · NCI · DANA-FARBER CANCER INST · PI POLYAK, KORNELIA · 2020 to 2024
$8.6MRegulation of the cell proliferation by CRL ubiquitin ligases-diversity supplementR35GM136250 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MICHELE PAGANO · 2020 to 2026
$2.7MNovel therapeutic approaches with CDK4/6 inhibitors for melanoma treatmentR01CA236226 · NCI · DANA-FARBER CANCER INST · PI SICINSKI, PETER · 2019 to 2023
$2.4MCDC7 kinase in normal and cancer cells: potential implications for cancer treatmentR01CA247375 · NCI · DANA-FARBER CANCER INST · PI SICINSKI, PETER · 2020 to 2024
$2.3MNCI NIH HHS P01 CA092584NCI NIH HHS P01 CA250959NCI NIH HHS P50 CA168504NCI NIH HHS R01 CA236226NCI NIH HHS R01 CA247375NIGMS NIH HHS R35 GM136250
Abstract
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.
Indexed as
CyclinsDNA Mismatch RepairAnimalsCyclin-Dependent Kinase Inhibitor p21InterphaseMammalsProliferating Cell Nuclear AntigenCyclin-Dependent Kinase Inhibitor p21CyclinsProliferating Cell Nuclear AntigenAMBRA1base excision repairCDK4cell cyclecullin-RING ubiquitin ligasescyclin D1DNA repairDNA repair pathway choiceD-type cyclinsG0 DNA repairG1 DNA repairgenome stabilitymismatch repairoxidative DNA damagePCNA
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.