Niels Keijzer
nkeijzer.bsky.social
Niels Keijzer
@nkeijzer.bsky.social
PhD student at the Netherlands Cancer Institute | Biochemistry & Structural Biology
I'm very proud that our paper, and with that the main project of my PhD, has just been published by @natcomms.nature.com! 🎉
Here, we reveal the unique, molecular mechanism by which USP1/UAF1 cleaves ubiquitin chains on PCNA, which may direct DNA damage tolerance.

doi.org/10.1038/s414...
USP1/UAF1 targets polyubiquitinated PCNA with an exo-cleavage mechanism that can temporarily enrich for monoubiquitinated PCNA - Nature Communications
DNA damage tolerance is regulated by ubiquitination of PCNA. Here, the authors present kinetic and structural studies showing that USP1/UAF1 prefers trimming K63- and K48-ubiquitin chains down over cl...
doi.org
July 31, 2025 at 11:53 AM
I figured the previous mysterious image deserved an upgrade!

USP1/UAF1's exo-cleavage mechanism, and its preference for polyubiquitinated PCNA, may drive DNA damage tolerance pathway choice by enriching for monoubiquitinated PCNA.

Read our preprint for our full analysis:
doi.org/10.1101/2024...
December 20, 2024 at 1:55 PM
Excited to share our new paper!

Here we reveal USP1/UAF1 as a highly efficient DUB for K63- and K48 polyubiquitinated PCNA and give detailed insights into its mechanism that may drive pathway choice in DNA damage tolerance.

Preprint is available now:
www.biorxiv.org/content/10.1...
USP1/UAF1 targets polyubiquitinated PCNA with an exo-cleavage mechanism that enriches for monoubiquitinated PCNA
DNA damage tolerance (DDT) is an important pathway that allows our cells to bypass DNA lesions during replication. DDT is orchestrated by ubiquitination of PCNA: Monoubiquitination (PCNA-Ub) initiates...
www.biorxiv.org
December 17, 2024 at 11:03 AM
Reposted by Niels Keijzer
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November 19, 2024 at 10:55 AM