Related Experiment Video
Updated: Mar 26, 2026

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
Published on: January 14, 2016
Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression
André Franz1, Paul A Pirson1, Domenic Pilger1,2
1Institute for Genetics and CECAD Research Center, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
Abstract:
The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging.
More Related Videos
08:53Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
Published on: May 2, 2025
10:32Detection of Post-Replicative Gaps Accumulation and Repair in Human Cells Using the DNA Fiber Assay
Published on: February 3, 2022
Related Concept Videos
Restarting Stalled Replication Forks
Restarting Stalled Replication Forks
The DNA Replication Fork
The DNA Replication Fork
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle