Silent information regulator type 2 (Sirtuin 2 or SIRT2) is a highly evolutionarily conserved NAD+ dependent deacetylase. SIRT2 is the only Sirtuin that acts in the cytosol. It expresses in almost all tissues, but most abundantly in the central nervous system. While SIRT2 is classified as a type III histone deacetylase, it is also capable
Over 100 years ago, Otto Werner first characterized a recessive autosomal disorder that caused premature, but largely typical, aging in adults, starting by the 3rd decade and resulting in death by the 6th decade via myocardial infarction or cancer. This disease, now known as Werner syndrome, is caused by specific alterations in the 162 KDa
SARS-CoV-2 virus (Covid-19) possesses one of the largest genomes of any RNA virus. While it naturally encodes structural proteins among its 29 genes, it also produces non-structural proteins that are necessary to perpetuate infection. Non-structural protein 16 (NSP16) is one such protein.1 NSP16 Camouflages Viral mRNA NSP16 is an m7GpppA-specific, S-adenosyl-L-methionine-dependent 2’-O-methyltransferase (2’-O-MTase) that “caps”
The most well-known and widely studied mechanisms of double-stranded DNA break (DSB) repairs are homologous recombination (HR) and classical non-homologous end joining (C-NHEJ). HR is almost error-free due to formatting by the homologous sister chromosome. C-NHEJ relies on direct ligation of double-stranded DNA ends and only ever presents errors at the junction points. Recently, a
Poly (ADP-ribose) glycohydrolase (PARG), along with poly (ADP-ribose) polymerase 1 (PARP1) are the principal elements of the DNA damage response (DDR). When single-strand breaks occur in cellular DNA, PARP1 mediates the poly ADP ribosylation of itself and target proteins, such as histones, promoting the decompaction of chromatin and recruiting relevant enzymes to initiate DNA repair.
Helicases are among the largest and most highly conserved families of enzymatic proteins in eukaryotic organisms. These proteins utilize NTP hydrolysis (usually ATP) to drive their recognition, remodeling, and response to target DNA or RNA.1 Nearly every aspect of nucleic acid metabolism is mediated by helicases. DNA helicases function in replication, repair, recombination, transcription, chromosome
RAF1, also known as c-Raf, is a member of the Raf family of ubiquitous serine/threonine kinases that regulate several critical biological processes, such as proliferation, differentiation, apoptosis, and metabolism. It functions as an activator of the mitogen-activated protein kinase (MAPK)/ ERK kinase (MEK) signaling pathway and a key effector of the small G protein Ras.
OAS1 (Oligoadenylate synthetase 1) is induced by type 1 interferon signaling. It recognizes 18 bp (or longer) double stranded RNA segments from invading viruses in the cytosol and catalyzes the production of 2’-5’ linked oligoadenylate (2-5A) from ATP. The 2-5A then, at the expense of yet more ATP, exclusively activates endoribonclease L (RNase L) by
DDX41 [DEAD (Asp-Glu-Ala-Asp) Box Polypeptide 41] is a cytosolic helicase sensor for dsDNA, DNA/RNA complexes, and cyclic dinucleotides (CDNs). Its N-terminal domain is responsible for translocation from the cytoplasm to the nucleus. Its DEAD domain, with its signature aspartate-glutamate-alanine-aspartate motif, is important for ATP-powered DNA/CDN detection and signaling. The remaining C-terminal domain functions as a
ALPK1 (Alpha Kinase 1) is an atypical serine/threonine-protein kinase that specifically detects and binds the pathogen-associated pattern metabolites (PAMPs), ADP-beta-D-manno-heptose (Beta-ADP-Heptose) or D-glycero-beta-D-manno-heptose 1,7-bisphosphate (HBP). These metabolic precursors of lipopolysaccharide (LPS) biosynthesis are present in all Gram-negative and some Gram-positive bacteria. This interaction stimulates ALPK1 to phosphorylate and activate TIFA, initiating an innate immune response