Dataset Information

Nuclear cGAS: guard or prisoner?

ABSTRACT: cGAS, an innate immune sensor of cellular stress, recognizes double-stranded DNA mislocalized in the cytosol upon infection, mitochondrial stress, DNA damage, or malignancy. Early models suggested that cytosolic localization of cGAS prevents autoreactivity to nuclear and mitochondrial self-DNA, but this paradigm has shifted in light of recent findings of cGAS as a predominantly nuclear protein tightly bound to chromatin. This has raised the question how nuclear cGAS is kept inactive while being surrounded by chromatin, and what function nuclear localization of cGAS may serve in the first place? Cryo-EM structures have revealed that cGAS interacts with nucleosomes, the minimal units of chromatin, mainly via histones H2A/H2B, and that these protein-protein interactions block cGAS from DNA binding and thus prevent autoreactivity. Here, we discuss the biological implications of nuclear cGAS and its interaction with chromatin, including various mechanisms for nuclear cGAS inhibition, release of chromatin-bound cGAS, regulation of different cGAS pools in the cell, and chromatin structure/chromatin protein effects on cGAS activation leading to cGAS-induced autoimmunity.

SUBMITTER: de Oliveira Mann CC

PROVIDER: S-EPMC8365253 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nuclear cGAS: guard or prisoner?

de Oliveira Mann Carina C CC Hopfner Karl-Peter KP

The EMBO journal 20210712 16

cGAS, an innate immune sensor of cellular stress, recognizes double-stranded DNA mislocalized in the cytosol upon infection, mitochondrial stress, DNA damage, or malignancy. Early models suggested that cytosolic localization of cGAS prevents autoreactivity to nuclear and mitochondrial self-DNA, but this paradigm has shifted in light of recent findings of cGAS as a predominantly nuclear protein tightly bound to chromatin. This has raised the question how nuclear cGAS is kept inactive while being ...[more]

PMID: 34250619

Similar Datasets

Project description:In 2011, a historic Supreme Court decision mandated that the state of California substantially reduce its prison population to alleviate overcrowding, which was deemed so severe as to preclude the provision of adequate healthcare. To comply, California passed the Public Safety Realignment Act (Assembly Bill [AB] 109), representing the largest ever court-ordered reduction of a prison population in U.S. history. AB109 was successful in reducing the state prison population; however, although the policy was precipitated by inadequate healthcare in state prisons, no studies have examined its effects on prisoner health. As other states grapple with overcrowded prisons and look to California's experience with this landmark policy, understanding how it may have impacted prisoner health is critical. We sought to evaluate the effects of AB109 on prison mortality and assess the extent to which policy-induced changes in the age distribution of prisoners may have contributed to these effects. To do so, we used prison mortality data from the Bureau of Justice Statistics and the California Deaths in Custody reporting program and prison population data from the National Corrections Reporting Program to examine changes in overall prison mortality, the age distribution of prisoners, and age-adjusted prison mortality in California relative to other states before and after the implementation of AB109. Following AB109, California prisons experienced an increase in overall mortality relative to other states that attenuated within three years. Over the same period, California experienced a greater upward shift in the age distribution of its prisoners relative to other states, suggesting that the state's increase in overall mortality may have been driven by this change in age distribution. Indeed, when accounting for this differential change in age distribution, mortality among California prisoners exhibited a greater reduction relative to other states in the third year after implementation. As other states seek to reduce their prison populations to address overcrowding, assessments of California's experience with AB109 should consider this potential improvement in age-adjusted mortality.

Dataset Information

Nuclear cGAS: guard or prisoner?

Publications

Nuclear cGAS: guard or prisoner?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets