Asset Details
Do you wish to reserve the book?
Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response
Do you wish to request the book?
Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response
2021
Overview
ADP ribosylation is a reversible posttranslational modification mediated by poly(ADP-ribose)transferases (e.g., PARP1) and (ADP-ribosyl)hydrolases (e.g., ARH3 and PARG), ensuring synthesis and removal of mono-ADP-ribose or poly-ADP-ribose chains on protein substrates. Dysregulation of ADP ribosylation signaling has been associated with several neurodegenerative diseases, including Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. Recessive ADPRHL2/ ARH3 mutations are described to cause a stress-induced epileptic ataxia syndrome with developmental delay and axonal neuropathy (CONDSIAS). Here, we present two families with a neuropathy predominant disorder and homozygous mutations in ADPRHL2 . We characterized a novel C26F mutation, demonstrating protein instability and reduced protein function. Characterization of the recurrent V335G mutant demonstrated mild loss of expression with retained enzymatic activity. Although the V335G mutation retains its mitochondrial localization, it has altered cytosolic/nuclear localization. This minimally affects basal ADP ribosylation but results in elevated nuclear ADP ribosylation during stress, demonstrating the vital role of ADP ribosylation reversal by ARH3 in DNA damage control.
Publisher
Life Science Alliance,Life Science Alliance LLC
Subject
/ ADP-Ribosylation - physiology
/ Adult
/ Age
/ Alleles
/ Amyotrophic lateral sclerosis
/ Ataxia
/ Atrophy
/ Brain
/ Enzymes
/ Epilepsy
/ Family
/ Female
/ Glycoside Hydrolases - genetics
/ Glycoside Hydrolases - metabolism
/ Humans
/ Legs
/ Male
/ Mutation
/ Patients
/ Pedigree
/ Poly (ADP-Ribose) Polymerase-1
/ Poly Adenosine Diphosphate Ribose - metabolism
/ Proteins
/ Walking
