Related Experiment Video
Updated: Aug 13, 2025

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Mammalian life depends on two distinct pathways of DNA damage tolerance
Olimpia Alessandra Buoninfante1, Bas Pilzecker1, Aldo Spanjaard1
1Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands.
Abstract:
DNA damage threatens genomic integrity and instigates stem cell failure. To bypass genotoxic lesions during replication, cells employ DNA damage tolerance (DDT), which is regulated via PCNA ubiquitination and REV1. DDT is conserved in all domains of life, yet its relevance in mammals remains unclear. Here, we show that inactivation of both PCNA-ubiquitination and REV1 results in embryonic and adult lethality, and the accumulation of DNA damage in hematopoietic stem and progenitor cells (HSPCs) that ultimately resulted in their depletion. Our results reveal the crucial relevance of DDT in the maintenance of stem cell compartments and mammalian life in unperturbed conditions.
More Related Videos
Related Concept Videos
Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
DNA Damage can Stall the Cell Cycle
Overview of DNA Repair
Chemically...
Fixing Double-strand Breaks
Homologous Recombination
Long-patch Base Excision Repair

