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
While most researchers are familiar with canonical DNA structures, primarily B (but also even A or Z) DNA, an even more exotic form exerts a vast influence over nearly every aspect of nucleic acid function. In both DNA and RNA, tracts of guanine with at least four consecutive members can self-associate via Hoogsten base pairing
MAPK14 (or p38 alpha or SAPK2a) is a proline-directed serine/threonine kinase activated by environmental stress or inflammatory signaling. While it is a well-conserved eukaryotic gene in the mitogen-activated protein kinase family, MAPK14 doesn’t typically respond to mitogens. All the same, MAPK14 is critically involved in cardiac development, sex determination, innate and adaptive immunity, and cellular
PRMT5 is a type II arginine methyltransferase that dimethylates arginine residues symmetrically. Its various functions extend into T cell development, B cell regulation, hematopoiesis, and mitotic control. In the past, research on PRMT5 primarily focused on cancer and the adaptive immune response. These are both situations where metabolism and growth are critical. Recent reports implicate
IRE1 (Inositol-Requiring Enzyme 1) is one of three resident transmembrane endoplasmic reticulum (ER) proteins that sense and signal distress from improper protein synthesis and conformation. (While IRE1 alpha is almost universally expressed and IRE1 beta is confined to the gut, both will be conflated as IRE1 here.) Secreted and transmembrane proteins are primarily produced in