Gergely Rona, Bearach Miwatani-Minter, Qingyue Zhang, Hailey V Goldberg, Marc A Kerzhnerman, Jesse B Howard, Daniele Simoneschi, Ethan Lane, John W Hobbs, Elizabeth Sassani, Andrew A Wang, Sarah Keegan, Daniel J Laverty, Cortt G Piett, Lorinc S Pongor, Miranda Li Xu, Joshua Andrade, Anish Thomas, Piotr Sicinski, Manor Askenazi, Beatrix Ueberheide, David Fenyö, Zachary D Nagel, Michele Pagano
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...
February 29, 2024: Molecular Cell