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SUMMARY:Unravelling the poly(ADP-ribose) code: How the structural diversit
 y of the post-translational modification poly(ADP-ribose) affects biochemi
 cal and biological processes
DTSTART:20201215T150000
DTEND:20201215T161500
DTSTAMP:20260508T082108Z
UID:87c9340d1e63c92b84ef26894f9fa391c1bd9d1e5657d1a895a2b0e7
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Aswin Mangerich (Universität Konstanz)\nPoly(ADP-ribosy
 l)ation (PARylation) is an essential post-translational modification (PTM)
 \, which is formed by poly(ADP-ribose) polymerases (PARPs). PARPs use NAD+
  as a substrate to modify target proteins with the nucleic-acid-like biopo
 lymer poly(ADP-ribose) (PAR)\, with variable branching frequencies and cha
 in lengths. Covalent modification as well as non-covalent PAR binding regu
 late physico-chemical properties of hundreds of target proteins\, thereby 
 modifying their enzymatic activities\, localization\, and macromolecular i
 nteractions. Importantly\, PARylation represents a fully reversible and hi
 ghly dynamic PTM\, because shortly after being synthesized\, PAR is rapidl
 y hydrolyzed by PAR-catabolizing enzymes. Thereby\, PARylation acts as a k
 ey mediator and regulator of cellular stress response on multiple levels. 
 Thus\, it is involved in genome maintenance\, chromatin remodeling\, gene 
 transcription\, RNA metabolism\, cell cycle control\, cellular energy meta
 bolism\, inflammation and the regulation of cell death (see Figure). On th
 e organismic level\, this leads to pleiotropic functions of PARylation in 
 physiology and pathophysiology\, in particular\, in processes related to c
 ancer and aging. This has important translational implications: On the one
  hand\, several pharmacological PARP inhibitors have been approved for the
  treatment of specific types of cancers\, i.e.\, following the concept of 
 synthetic lethality. On the other hand\, molecules that increase levels of
  PARPs’ substrate NAD+ in vitro and in vivo\, so-called NAD+ boosters\, 
 are being tested for therapeutic effects on age-related diseases in severa
 l organisms including humans.\nIn this talk\, I will cover our recent inve
 stigations on how the structural diversity of poly(ADP-ribose) molecules w
 ith respect to chain lengths and branching frequencies affects biochemical
  and biological processes.
LOCATION:https://epfl.zoom.us/j/83488461124
STATUS:CONFIRMED
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