The Biochemical Society 2027 Centenary Award presented to Professor Matthew Freeman from University of Oxford, UK.

A leader in the cell biology of signalling, the 2027 Centenary Award is presented to Matthew Freeman in recognition of his pioneering discoveries into the biological significance and mechanisms of rhomboid intramembrane proteases and pseudoprotease and unwavering commitment to mentorship!

We show that the E3 ubiquitin ligase DTX2 creates a dual hybrid ADP-ribosyl-ubiquitin mark (ADPr-Ub) at DNA damage sites, driving the recruitment of RNF114, RNF138, and RNF166 proteins independently of HPF1.
journals.plos.org/plosbiology/...

FEBS Press Sorbitol-induced hyperosmotic stress rapidly induces reversible mono(ADP-ribosyl)ation (MARylation) on PARP1 without the signs of genotoxic signaling. We show that PARP1 autoMARylation is HPF1 depend...

Hyperosmotic stress induces PARP1-mediated HPF1-dependent mono(ADP-ribosyl)ation:
febs.onlinelibrary.wiley.com/doi/10.1002/...

Reversible RNA ADP-ribosylation on uracil bases Abstract. ADP-ribosylation is a conserved modification that uses NAD+ as a co-substrate to regulate essential cellular processes, such as genome stability

In this paper, we present the first evidence suggesting that reversible RNA ADP-ribosylation on bases occurs in higher organisms (through the combined action of PARP10 and TARG1):
academic.oup.com/nar/article/...

Check out our new review on PARP14. We cover everything to know about this fascinating enzyme—its structure and evolution, antiviral activities against coronavirus infection, roles in genome stability and inflammation, and its links to ubiquitination signaling.
genesdev.cshlp.org/content/earl...

New research from #OpenBiology: Histidine and tyrosine residues are targets for SIRT6 ADP-ribosylation activity royalsocietypublishing.org/rsob/article... | #Biochemistry

Histidine and tyrosine residues are targets for SIRT6 ADP-ribosylation activity Abstract. SIRT6, a highly conserved member of the sirtuin family, plays a critical role in diverse cellular processes, including gene regulation, DNA damag

In this paper, we demonstrate that the sirtuin SIRT6 can efficiently ADP-ribosylate histidine and tyrosine residues in proteins.
royalsocietypublishing.org/rsob/article...

Recent discovery have revealed reversible ADP-ribosylation of cytosine bases in nucleic acids:
www.mdpi.com/2072-6651/18...

The PARG frontier: mechanisms of PAR turnover and opportunities in precision oncology ADP-ribosylation is a versatile post-translational modification that governs fundamental processes, including DNA repair, transcription, and stress ad…

Excited to share our lab’s new article in Biochemical Pharmacology on PARG as a key regulator opposing PARP functions and its emerging therapeutic potential in cancer. Overview of current PARG inhibitors included. www.sciencedirect.com/science/arti...

Did you miss the original abstract deadline? No worries, we’ve extended it to January 30th! Don’t miss your chance to be part of an exciting meeting highlighting the cutting edge of the field.

The first chemical synthesis of ADP-ribosylated oligonucleotides provides powerful tools to study ADP-ribosylation of nucleic acids:
pubs.acs.org/doi/10.1021/...

Synthesis of Adenosine Diphosphate Ribose Histidine Adenosine diphosphate ribosylated histidine (His-ADPr) is a vital signaling molecule for the bacterial immune system, the antiphage system in particular. In this unique second messenger molecule, the distal nitrogen of the histidine side chain is ribosylated in a β fashion. Here, we describe the synthesis of this bacterial metabolite and its triazole isostere and evaluate the stability of His-ADPr to relevant ribosyl hydrolases.

We contributed to this newly published article describing the chemical synthesis of ADP-ribosylated histidine, which serves as a signalling molecule in bacterial antiphage systems:
pubs.acs.org/doi/10.1021/...

PARG regulates the proteasomal degradation of TARG1 ADP-ribosylation (ADPr) is a reversible modification of macromolecules critical for the regulation of genome stability, stress responses, and proteost…

Learn more about the interplay between ADP-ribosylation and ubiquitination: PARG regulates proteasomal degradation of the ADP-ribosyl hydrolase TARG1 by preventing PAR-dependent ubiquitination mediated by the E3 ligases HUWE1 and TRIP12
www.sciencedirect.com/science/arti...

Mono-ADP-ribosylation as a degradation mark?
@andriigorelik.bsky.social, Ivan Ahel et al observe increased ADP-ribosylation of aryl hydrocarbon receptor (AHR) & PARP7 upon ubiquitin-proteasome blockage, crosstalk with DTX2 E3, as rapid AHR-transcription off-switch
www.embopress.org/doi/full/10....

Ubiquitin pathway blockade reveals endogenous ADP-ribosylation marking PARP7 and AHR for degradation | The EMBO Journal imageimageDegradation mechanisms of transcriptionally active aryl hydrocarbon receptor (AHR) are unclear. This work reveals that PARP7 ADP-ribosylates itself and ligand-bound AHR, creating a recogniti...

The interplay between ADP-ribosylation and ubiquitination, mediated by PARP7 and DTX2 proteins, can serve as a rapid AHR transcription “off-switch” through proteasomal degradation.
www.embopress.org/doi/full/10....

Akin to bacterial SIR2 antiphage proteins, human SIRal, also known as FAM118b, forms filaments that are essential for its NAD processing activity.

Awesome to see structures of these filaments that differ from bacterial ones.

Congrats to the authors on this beautiful study.

Filament formation and NAD processing by noncanonical human FAM118 sirtuins Nature Structural & Molecular Biology - Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that...

Very happy to share our collaborative project on FAM118 proteins - noncanonical sirtuins that form filaments and process NAD in human and other vertebrate cells.

Filament formation and NAD processing by noncanonical human FAM118 sirtuins - Nature Structural & Molecular Biology Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that FAM118A/B processing of NAD involves head-to-tail filament...

Please check our collaborative paper with Marcin Suskiewicz and Sebastien Huet labs on FAM118 proteins – non-canonical sirtuins that form filaments and act as NADases in human and other vertebrate cells.
www.nature.com/articles/s41...

Histone PARylation factor 1: a review of its role in the DNA damage response Abstract. Although poly-(ADP ribose) polymerase 1 (PARP1) and PARylation of histones have been known for over 50 years and have been successfully targeted

Beautiful review from J. Rudolph on Histone PARylation factor 1: a review of its role in the DNA damage response url: academic.oup.com/nar/article/...

Converting a kinase through molecular mimicry - Dunn School Published in EMBO Reports, a new study by the Thurston Group reveals how a small virulence protein from Salmonella called SteE, uses molecular mimicry to reprogramme host kinase specificity.

A new study by @thurstonlab.bsky.social reveals how a small virulence protein from Salmonella uses molecular mimicry to reprogramme host kinase specificity.

Find out more: www.path.ox.ac.uk/news-article...

Here you can read our full review paper on the interplay between ADP-ribosylation and ubiquitination, with special focus on dual, hybrid modification ADPr-Ub:
pubmed.ncbi.nlm.nih.gov/41065402/

This News & Views article provides a nice overview of the recent discoveries that RNF114 recognizes a dual modification ADP-ribose–ubiquitin (ADPr-Ub) and subsequently extends it by adding additional ubiquitin units.:
pubmed.ncbi.nlm.nih.gov/41039156/

RNF114 and RNF166 exemplify a new E3 ligases family that recognizes #MARUbylation –hybrid ADP-ribose/ubiquitin modifications– and extends them with K11-linked polyubiquitin
@jnpruneda.bsky.social @michaelnadbio.bsky.social and colleagues
www.embopress.org/doi/full/10....

The September @natsmb.nature.com issue is out! www.nature.com/articles/s41...
We feature very interesting papers on ubiquitylation and degradation. Really excited to continue to serve the proteostasis and PTMs communities and publish conceptually insightful work.

Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes - Nature Biotechnology Append editing of ADP-ribosyl to thymine is used for precise modifications in bacteria and eukaryotes.

Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes - @helmholtz-hiri.bsky.social go.nature.com/4n7zDpG

Applications now open for our PhD studentship programme - Dunn School Applications are now open to apply for our four year, fully-funded PhD programme in Molecular Cell Biology in Health and Disease.

Our PhD studentship programme is officially open; pass it on

If you are looking for a fully-funded PhD in the mechanisms underlying human disease, here are the details...

Great science and a great environment!

www.path.ox.ac.uk/news-article...

The rise of ADP-ribose–ubiquitin Nature Structural & Molecular Biology - Post-translational modifications show mechanistic crosstalk, exemplified by the ADP-ribose–ubiquitin hybrid signal, in which one post-translational...

A few years back we discovered a dual hybrid protein modification composed of an ADP-ribose dinucleotide and the ubiquitin moieties (ADPr-Ub). Here you can read our review that will give you an update on this increasingly popular topic:
rdcu.be/eETIT

We have postdoc positions available to study roles of ADP-ribosylation and ubiquitination signalling in genome stability, infection or immunity. Please enquire if you are interested.

📣 Applications now open 📣

We are seeking outstanding ECRs looking for a stimulating and supportive environment in which to establish their research group as externally-funded fellows, in any area or cell or molecular biology underlying disease!

Please share!

www.path.ox.ac.uk/work-with-us...

Postdoctoral Fellow - Costa Lab Salary for this Role: From £45,500 with benefits, subject to skills and experience. Job Title: Postdoctoral Fellow - Costa Lab Reports to: Alessandro Costa Closing Date: 03/Aug/2025 23.59 GMT Job Desc...

Less than two weeks left to apply!

Postdoc positions in my lab to study

1. initiation of DNA replication.

2. chromatin replication/epigenetic inheritance.

Great for biochemists, biophysicists & structural biologists.

Deadline 3 August 2025.

crick.wd3.myworkdayjobs.com/External/job...