Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair.

TitleLamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair.
Publication TypeJournal Article
Year of Publication2021
AuthorsMurray-Nerger, LA, Justice, JL, Rekapalli, P, Hutton, JE, Cristea, IM
JournalNucleic Acids Res
Volume49
Issue4
Pagination2044-2064
Date Published2021 02 26
ISSN1362-4962
KeywordsAcetylation, 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>

DOI10.1093/nar/gkab019
Alternate JournalNucleic Acids Res
PubMed ID33533922
PubMed Central IDPMC7913768
Grant ListR01 GM114141 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States