The DNA damage response at eroded telomeres and tethering to the nuclear pore complex

2009 ◽  
Vol 11 (8) ◽  
pp. 980-987 ◽  
Author(s):  
Basheer Khadaroo ◽  
M. Teresa Teixeira ◽  
Pierre Luciano ◽  
Nadine Eckert-Boulet ◽  
Susanne M. Germann ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Nuclear Pore Complex ◽  
Nuclear Pore ◽  
Damage Response

scholarly journals Inhibition of HIV infection by structural proteins of the inner nuclear membrane is associated with reduced chromatin dynamics

2020 ◽  
Author(s):  
Anvita Bhargava ◽  
Mathieu Maurin ◽  
Patricia M. Davidson ◽  
Mabel Jouve ◽  
Xavier Lahaye ◽  
...  
Keyword(s):  
Dna Damage ◽  
Hiv Infection ◽  
Nuclear Envelope ◽  
Dna Damage Response ◽  
Hela Cells ◽  
Nuclear Pore ◽  
Lamin A ◽  
Damage Response ◽  
Hiv 1

AbstractThe Human Immunodeficiency Virus (HIV) enters the nucleus to establish infection. HIV interacts with nuclear pore components to cross the nuclear envelope. In contrast, the role of other proteins of the nuclear envelope in HIV infection is not yet understood. The inner nuclear transmembrane proteins SUN1 and SUN2 connect lamins in the interior of the nucleus to the cytoskeleton in the cytoplasm. Increased levels of SUN1 or SUN2 potently restrict HIV infection through an unresolved mechanism. Here, we find that SUN1 and SUN2 exhibit a differential and viral strain-specific antiviral activity HIV-1 and HIV-2. In macrophages and HeLa cells, HIV-1 and HIV-2 are respectively preferentially inhibited by SUN1 and SUN2. This specificity maps to the nucleoplasmic domain of SUN proteins, which associates with Lamin A/C and participates to the DNA damage response. We find that etoposide, a DNA-damaging drug, stimulates infection. Inhibition of the DNA damage signaling kinase ATR, which induces a DNA damage response, also enhances HIV-1 infection. The proviral effect of ATR inhibition on infection requires the HIV-1 Vpr gene. Depletion of endogenous Lamin A/C, which sensitizes cells to DNA damage, also enhances HIV-1 infection in HeLa cells. SUN1 overexpression neutralizes these proviral effects, while the antiviral effect of SUN2 is rescued by etoposide treatment. Finally, we show that inhibition of HIV-1 infection by overexpressed SUN proteins and endogenous Lamin A/C is associated with reduced internal movements of chromatin and reduced rotations of the nucleus. Altogether, these results highlight distinct antiviral activities of SUN1 and SUN2 and reveal an emerging role of nuclear movements and the DNA damage response in the control of HIV infection by structural components of the nuclear envelope.

scholarly journals Posttranslational marks control architectural and functional plasticity of the nuclear pore complex basket

2016 ◽  
Vol 212 (2) ◽  
pp. 167-180 ◽  
Author(s):  
Carlos A. Niño ◽  
David Guet ◽  
Alexandre Gay ◽  
Sergine Brutus ◽  
Frédéric Jourquin ◽  
...  
Keyword(s):  
Dna Damage Response ◽  
Nuclear Pore Complex ◽  
Posttranslational Modifications ◽  
Genotoxic Stress ◽  
Molecular Organization ◽  
Genome Integrity ◽  
Nuclear Pore ◽  
Functional Constraints ◽  
Damage Response

The nuclear pore complex (NPC) serves as both the unique gate between the nucleus and the cytoplasm and a major platform that coordinates nucleocytoplasmic exchanges, gene expression, and genome integrity. To understand how the NPC integrates these functional constraints, we dissected here the posttranslational modifications of the nuclear basket protein Nup60 and analyzed how they intervene to control the plasticity of the NPC. Combined approaches highlight the role of monoubiquitylation in regulating the association dynamics of Nup60 and its partner, Nup2, with the NPC through an interaction with Nup84, a component of the Y complex. Although major nuclear transport routes are not regulated by Nup60 modifications, monoubiquitylation of Nup60 is stimulated upon genotoxic stress and regulates the DNA-damage response and telomere repair. Together, these data reveal an original mechanism contributing to the plasticity of the NPC at a molecular-organization and functional level.

2118-P: Regulation of Ataxia-Telangiectasia and Rad3-Related (ATR)–Dependent DNA Damage Response by Nitric Oxide in ß-Cells

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2118-P
Author(s):  
CHAY TENG YEO ◽  
BRYNDON OLESON ◽  
JOHN A. CORBETT ◽  
JAMIE K. SCHNUCK
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Damage Response

DNA damage response and neuroprotection

10.2741/2862 ◽  
2008 ◽  
Vol 13 (13) ◽  
pp. 2504 ◽  
Author(s):  
Inna, I. Kruman
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response
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