Title | Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Murray-Nerger, LA, Justice, JL, Rekapalli, P, Hutton, JE, Cristea, IM |
Journal | Nucleic Acids Res |
Volume | 49 |
Issue | 4 |
Pagination | 2044-2064 |
Date Published | 2021 Feb 26 |
ISSN | 1362-4962 |
Keywords | Acetylation, Cell Line, Cell Nucleus, Chromatin, DNA Damage, DNA Repair, Female, G1 Phase Cell Cycle Checkpoints, Herpesvirus 1, Human, Humans, Lamin Type B, Lysine, Nuclear Lamina, Tumor Suppressor p53-Binding Protein 1 |
Abstract | <p>The integrity and regulation of the nuclear lamina is essential for nuclear organization and chromatin stability, with its dysregulation being linked to laminopathy diseases and cancer. Although numerous posttranslational modifications have been identified on lamins, few have been ascribed a regulatory function. Here, we establish that lamin B1 (LMNB1) acetylation at K134 is a molecular toggle that controls nuclear periphery stability, cell cycle progression, and DNA repair. LMNB1 acetylation prevents lamina disruption during herpesvirus type 1 (HSV-1) infection, thereby inhibiting virus production. We also demonstrate the broad impact of this site on laminar processes in uninfected cells. LMNB1 acetylation negatively regulates canonical nonhomologous end joining by impairing the recruitment of 53BP1 to damaged DNA. This defect causes a delay in DNA damage resolution and a persistent activation of the G1/S checkpoint. Altogether, we reveal LMNB1 acetylation as a mechanism for controlling DNA repair pathway choice and stabilizing the nuclear periphery.</p> |
DOI | 10.1093/nar/gkab019 |
Alternate Journal | Nucleic Acids Res |
PubMed ID | 33533922 |
PubMed Central ID | PMC7913768 |
Grant List | R01 GM114141 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States |