scholarly journals DNA damage repair machinery and HIV escape from innate immune sensing

2014 ◽  
Vol 5 ◽  
Author(s):  
Christelle Brégnard ◽  
Monsef Benkirane ◽  
Nadine Laguette
Keyword(s):  
Dna Damage ◽  
Dna Damage Repair ◽  
Innate Immune ◽  
Damage Repair ◽  
Immune Sensing ◽  
Innate Immune Sensing

scholarly journals Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS

2019 ◽  
Vol 216 (5) ◽  
pp. 1199-1213 ◽  
Author(s):  
Matthieu Gratia ◽  
Mathieu P. Rodero ◽  
Cécile Conrad ◽  
Elias Bou Samra ◽  
Mathieu Maurin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Genome Instability ◽  
Bloom Syndrome ◽  
Innate Immune ◽  
Genome Integrity ◽  
Immune Sensing ◽  
Syndrome Protein ◽  
Innate Immune Sensing ◽  
Exonuclease Trex1

Cellular innate immune sensors of DNA are essential for host defense against invading pathogens. However, the presence of self-DNA inside cells poses a risk of triggering unchecked immune responses. The mechanisms limiting induction of inflammation by self-DNA are poorly understood. BLM RecQ–like helicase is essential for genome integrity and is deficient in Bloom syndrome (BS), a rare genetic disease characterized by genome instability, accumulation of micronuclei, susceptibility to cancer, and immunodeficiency. Here, we show that BLM-deficient fibroblasts show constitutive up-regulation of inflammatory interferon-stimulated gene (ISG) expression, which is mediated by the cGAS–STING–IRF3 cytosolic DNA–sensing pathway. Increased DNA damage or down-regulation of the cytoplasmic exonuclease TREX1 enhances ISG expression in BLM-deficient fibroblasts. cGAS-containing cytoplasmic micronuclei are increased in BS cells. Finally, BS patients demonstrate elevated ISG expression in peripheral blood. These results reveal that BLM limits ISG induction, thus connecting DNA damage to cellular innate immune response, which may contribute to human pathogenesis.

scholarly journals Human Papillomaviruses Target the DNA Damage Repair and Innate Immune Response Pathways to Allow for Persistent Infection

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1390
Author(s):  
Elona Gusho ◽  
Laimonis Laimins
Keyword(s):  
Immune Response ◽  
Dna Damage ◽  
High Risk ◽  
Persistent Infection ◽  
Ataxia Telangiectasia ◽  
Dna Damage Repair ◽  
Immune Surveillance ◽  
Human Papillomaviruses ◽  
Innate Immune ◽  
Damage Repair

Persistent infection with high-risk human papillomaviruses (HPVs) is the major risk factor associated with development of anogenital and oropharyngeal cancers. Initial infection by HPVs occurs into basal epithelial cells where viral genomes are established as nuclear episomes and persist until cleared by the immune response. Productive replication or amplification occurs upon differentiation and is dependent upon activation of the ataxia-telangiectasia mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) DNA damage repair (DDR) pathways. In addition to activating DDR pathways, HPVs must escape innate immune surveillance mechanisms by antagonizing sensors, adaptors, interferons and antiviral gene expression. Both DDR and innate immune pathways are key host mechanisms that crosstalk with each other to maintain homeostasis of cells persistently infected with HPVs. Interestingly, it is still not fully understood why some HPV infections get cleared while others do not. Targeting of these two processes with antiviral therapies may provide opportunities for treatment of cancers caused by high-risk HPVs.

scholarly journals Genomic Instability and DNA Damage Repair Pathways Induced by Human Papillomaviruses

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1821
Author(s):  
Takeyuki Kono ◽  
Laimonis Laimins
Keyword(s):  
Dna Damage ◽  
Dna Damage Repair ◽  
Tumor Development ◽  
Human Papillomaviruses ◽  
Innate Immune ◽  
Genomic Integrity ◽  
Cytidine Deaminases ◽  
Damage Repair ◽  
Causative Agents ◽  
Apobec3 Family

Human papillomaviruses (HPV) are the causative agents of cervical and other anogenital cancers as well as those of the oropharynx. HPV proteins activate host DNA damage repair factors to promote their viral life cycle in stratified epithelia. Activation of both the ATR pathway and the ATM pathway are essential for viral replication and differentiation-dependent genome amplification. These pathways are also important for maintaining host genomic integrity and their dysregulation or mutation is often seen in human cancers. The APOBEC3 family of cytidine deaminases are innate immune factors that are increased in HPV positive cells leading to the accumulation of TpC mutations in cellular DNAs that contribute to malignant progression. The activation of DNA damage repair factors may corelate with expression of APOBEC3 in HPV positive cells. These pathways may actively drive tumor development implicating/suggesting DNA damage repair factors and APOBEC3 as possible therapeutic targets.

366-OR: TCF19 Promotes Functional Beta-Cell Mass and Proliferative Capacity by Regulating DNA Damage Repair Pathways

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 366-OR
Author(s):  
GRACE H. YANG ◽  
JEE YOUNG HAN ◽  
SUKANYA LODH ◽  
JOSEPH T. BLUMER ◽  
DANIELLE FONTAINE ◽  
...  
Keyword(s):  
Dna Damage ◽  
Beta Cell ◽  
Dna Damage Repair ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Proliferative Capacity ◽  
Damage Repair ◽  
Repair Pathways
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