Genome homeostasis defects drive enlarged cells into senescence

• DOI: 10.1016/j.molcel.2023.10.018
• Publication Date: 2023-11-16T15:37:17Z
• Authors: Sandhya Manohar; Marianna E. Estrada; Federico Uliana; Karla Vuina; Patricia Moyano A...; Robertus A.M. de ...; Gabriel E. Neurohr
• Keywords: Senescence; Homeostasis

Cellular senescence refers to an irreversible state of cell-cycle arrest and plays important roles in aging cancer biology. Because is associated with increased cell size, we used reversible arrests combined growth rate modulation study how excessive affects proliferation. We find that enlarged cells upregulate p21, which limits progression. Cells re-enter the cycle encounter replication stress well tolerated physiologically sized but causes severe DNA damage cells, ultimately resulting mitotic failure permanent withdrawal. demonstrate fail recruit 53BP1 other non-homologous end joining (NHEJ) machinery sites robustly initiate damage-dependent p53 signaling, rendering them highly sensitive genotoxic stress. propose impaired response primes for persistent replication-acquired damage, leading division exit.