Related Experiment Video
Updated: Mar 18, 2026

Localization of SUMO-modified Proteins Using Fluorescent Sumo-trapping Proteins
Published on: April 27, 2019
USP7/HAUSP: A SUMO deubiquitinase at the heart of DNA replication
Veronique A J Smits1, Raimundo Freire1
1Unidad de Investigación, Hosptial Universitario de Canarias, Instituto de Tecnologías Biomédicas, La Laguna, Tenerife, Spain.
Abstract:
DNA replication is both highly conserved and controlled. Problematic DNA replication can lead to genomic instability and therefore carcinogenesis. Numerous mechanisms work together to achieve this tight control and increasing evidence suggests that post-translational modifications (phosphorylation, ubiquitination, SUMOylation) of DNA replication proteins play a pivotal role in this process. Here we discuss such modifications in the light of a recent article that describes a novel role for the deubiquitinase (DUB) USP7/HAUSP in the control of DNA replication. USP7 achieves this function by an unusual and novel mechanism, namely deubiquitination of SUMOylated proteins at the replication fork, making USP7 also a SUMO DUB (SDUB). This work extends previous observations of increased levels of SUMO and low levels of ubiquitin at the on-going replication fork. Here, we discuss this novel study, its contribution to the DNA replication and genomic stability field and what questions arise from this work.
Insights
The deubiquitinase USP7/HAUSP uniquely removes SUMOylation at replication forks, acting as a SUMO deubiquitinase (SDUB). This finding reveals a new mechanism controlling DNA replication and genomic stability.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA replication is a highly conserved and tightly regulated process crucial for genomic stability.
- Dysfunctional DNA replication can lead to genomic instability and carcinogenesis.
- Post-translational modifications, including phosphorylation, ubiquitination, and SUMOylation, are increasingly recognized as key regulators of DNA replication proteins.
Purpose of the Study:
- To discuss the novel role of the deubiquitinase USP7/HAUSP in DNA replication control.
- To highlight USP7's unique mechanism of deubiquitinating SUMOylated proteins at the replication fork.
- To explore the implications of USP7 acting as a SUMO deubiquitinase (SDUB) for DNA replication and genomic stability.
Main Methods:
- Literature review and discussion of a recent study on USP7/HAUSP.
- Analysis of post-translational modifications at the replication fork.
- Integration of findings with existing knowledge on SUMOylation and ubiquitination in DNA replication.
Main Results:
- USP7/HAUSP functions as a SUMO deubiquitinase (SDUB) at the replication fork.
- USP7's activity involves the removal of SUMOylated proteins during DNA replication.
- This mechanism contributes to the observed balance of SUMO and ubiquitin at ongoing replication forks.
Conclusions:
- USP7/HAUSP plays a novel and critical role in regulating DNA replication through SUMO deubiquitination.
- This discovery provides new insights into the mechanisms maintaining genomic stability.
- Further research is needed to fully elucidate the implications of USP7's SDUB activity.
More Related Videos
10:12Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
12:28Protein Purification Technique that Allows Detection of Sumoylation and Ubiquitination of Budding Yeast Kinetochore Proteins Ndc10 and Ndc80
Published on: May 3, 2015
Related Concept Videos
Restarting Stalled Replication Forks
Translesion DNA Polymerases
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
The DNA Replication Fork
The DNA Replication Fork
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle