Related Experiment Video

Updated: Jul 21, 2025

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage
10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

10.3K

PARP14 is a writer, reader, and eraser of mono-ADP-ribosylation

Archimede Torretta1, Constantinos Chatzicharalampous1, Carmen Ebenwaldner1

  • 1Department of Chemistry, Center for Molecular Protein Science (CMPS), Lund University, Lund, Sweden.

The Journal of Biological Chemistry
|July 28, 2023
PubMed

Insights

Researchers characterized PARP14 macrodomain-1 and found it has ADP-ribosyl glycohydrolase activity, similar to PARP9. This discovery impacts understanding of PARP14 and PARP9 roles in disease and therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Enzymology

Background:

  • Poly(ADP-ribose) polymerases (PARPs) are crucial enzymes in DNA repair and signaling.
  • PARP14/BAL2 is implicated in cancer, inflammation, and infection, with its domains targeted for therapy.
  • The function of PARP14 macrodomain-1 (MD1) was previously unclear, unlike MD2 and MD3.

Purpose of the Study:

  • To biochemically characterize the enzymatic activity of PARP14 MD1.
  • To investigate the homologous macrodomain-1 of PARP9.
  • To elucidate the functional role of these macrodomains in ADP-ribosylation.

Main Methods:

  • Biochemical assays measuring ADP-ribosylation levels.
  • Characterization of PARP14 MD1 and PARP9 MD1 activities.
  • Site-directed mutagenesis (F926A in PARP14, F244A in PARP9) to assess activity.

Main Results:

  • Both PARP14 MD1 and PARP9 MD1 exhibit ADP-ribosyl glycohydrolase activity.
  • This activity is not specific to protein side chains.
  • PARP14 MD1 does not degrade poly(ADP-ribose).
  • Mutations F926A (PARP14) and F244A (PARP9) significantly reduced glycohydrolase activity, indicating mechanistic similarity to SARS-CoV-2 Nsp3 Mac1.

Conclusions:

  • PARP14 MD1 and PARP9 MD1 are identified as novel human ADP-ribosyl glycohydrolases.
  • This finding adds to the known repertoire of human glycohydrolases.
  • The results necessitate a re-evaluation of how PARP14 and PARP9 functions are studied and understood in biological pathways and disease.
Keywords:
ADP-ribosylationADP-ribosyltransferasehydrolasemacrodomainpoly(ADP-ribose) polymerase (PARP)posttranslational modification (PTM)protein domainsignaling

More Related Videos

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

10.0K
Author Spotlight: Exploring the Frontier of mRNA Research with Poly A Tail Analysis Techniques08:16

Author Spotlight: Exploring the Frontier of mRNA Research with Poly A Tail Analysis Techniques

Published on: January 12, 2024

1.0K

Related Concept Videos

Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
8.3K
RNA Editing02:23

RNA Editing

RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.1K
Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
24.3K
Ribosome Profiling02:24

Ribosome Profiling

Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.6K
Protein Modifications in the RER01:26

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.3K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.2K