The functionality of DNA, RNA and proteins is altered dynamically in response to physiological and pathological cues, partly achieved by their modification. While the modification of proteins with ADP-ribose has been well studied, nucleic acids were only recently identified as substrates for ADP-ribosylation by mammalian enzymes. RNA and DNA can be ADP-ribosylated by specific ADP-ribosyltransferases such as PARP1–3, PARP10 and tRNA 2′-phosphotransferase (TRPT1). Evidence suggests that these enzymes display different preferences towards different oligonucleotides. These reactions are reversed by ADP-ribosylhydrolases of the macrodomain and ARH families, such as MACROD1, TARG1, PARG, ARH1 and ARH3. Most findings derive from in vitro experiments using recombinant components, leaving the relevance of this modification in cells unclear. In this Survey and Summary, we provide an overview of the enzymes that ADP-ribosylate nucleic acids, the reversing hydrolases, and the substrates’ requirements. Drawing on data available for other organisms, such as pierisin1 from cabbage butterflies and the bacterial toxin–antitoxin system DarT–DarG, we discuss possible functions for nucleic acid ADP-ribosylation in mammals. Hypothesized roles for nucleic acid ADP-ribosylation include functions in DNA damage repair, in antiviral immunity or as non-conventional RNA cap. Lastly, we assess various methods potentially suitable for future studies of nucleic acid ADP-ribosylation.
A methodology for the synthesis of 2H‐[1,3]oxazino[3,2‐α]indolin‐4(3H)‐ones is reported. They are obtained from readily available materials by a facile synthetic procedure following either a two‐step cascade reaction or a step‐by‐step transformation. The target compounds represent a hitherto unreported class of indole derivatives with a novel kind of tris‐ or tetracyclic backbone.
A large library of actin-associated proteins steer nucleation, cross-linking, capping, and elongation of actin filaments. The precise spatial and temporal co-ordination of these functions is fundamental for the movement of cells that is required for many biological events ranging from organ development to tissue repair. The importance of actin cytoskeleton dynamics
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