Proteomic Analyses of the Eukaryotic Replication Machinery
Overview
Authors
Affiliations
DNA replication in a human cell involves hundreds of proteins that copy the DNA accurately and completely each cell division cycle. In addition to the core DNA copying machine (the replisome), accessory proteins work to respond to replication stress, correct errors, and repackage the DNA into appropriate chromatin structures. New proteomic tools have been invented in the past few years to facilitate the purification, identification, and quantification of the replication, chromatin maturation, and replication stress response machineries. These tools, including iPOND (isolation of proteins on nascent DNA) and NCC (nascent chromatin capture), have yielded discoveries of new proteins involved in these processes and insights into the dynamic regulatory processes ensuring genome and chromatin integrity. In this review, I will introduce these experimental approaches and examine how they have been utilized to define the replication fork proteome.
Quantitative Chromatin Protein Dynamics During Replication Origin Firing in Human Cells.
Gadi S, Hendriks I, Nielsen C, Popova P, Hickson I, Nielsen M Mol Cell Proteomics. 2025; 24(3):100915.
PMID: 39880081 PMC: 11889381. DOI: 10.1016/j.mcpro.2025.100915.
The herpes simplex virus alkaline nuclease is required to maintain replication fork progression.
Mullon P, Maldonado-Luevano E, Mehta K, Mohni K J Virol. 2024; 98(12):e0183624.
PMID: 39508568 PMC: 11650972. DOI: 10.1128/jvi.01836-24.
Proteome profiling of polyomavirus nuclear replication centers using iPOND.
Erickson K, Langsfeld E, Holland A, Ebmeier C, Garcea R J Virol. 2024; 98(11):e0079024.
PMID: 39480110 PMC: 11575236. DOI: 10.1128/jvi.00790-24.
Ryder E, Nasir N, Durgan A, Jenkyn-Bedford M, Tye S, Zhang X Nucleic Acids Res. 2024; 52(20):12405-12421.
PMID: 39360622 PMC: 11551741. DOI: 10.1093/nar/gkae831.
Time-resolved interactome profiling deconvolutes secretory protein quality control dynamics.
Wright M, Timalsina B, Garcia Lopez V, Hermanson J, Garcia S, Plate L Mol Syst Biol. 2024; 20(9):1049-1075.
PMID: 39103653 PMC: 11369088. DOI: 10.1038/s44320-024-00058-1.