Related Experiment Video

Updated: Jan 31, 2026

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

3.6K

Mechanisms of DNA Damage Tolerance: Post-Translational Regulation of PCNA

Wendy Leung1, Ryan M Baxley2, George-Lucian Moldovan3

  • 1Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. leung086@umn.edu.

Genes
|December 28, 2018
PubMed

Insights

DNA damage tolerance (DDT) allows replication to continue past DNA lesions. Post-translational modifications (PTMs) of proliferating cell nuclear antigen (PCNA) regulate DDT pathways, ensuring genomic integrity during replication stress.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Genomic integrity is constantly challenged by DNA damage during replication.
  • DNA damage tolerance (DDT) mechanisms enable replication to proceed past DNA lesions.
  • Two main DDT pathways, translesion synthesis (TLS) and template switching (TS), exist.

Purpose of the Study:

  • To review the role of post-translational modifications (PTMs) of proliferating cell nuclear antigen (PCNA) in regulating DNA damage tolerance (DDT).
  • To discuss how PCNA PTMs control error-prone versus error-free DDT pathways.
  • To explore the involvement of PCNA PTMs in various cellular processes.

Main Methods:

  • Literature review focusing on PCNA post-translational modifications.
  • Analysis of the regulatory roles of ubiquitin and SUMOylation on PCNA.
  • Examination of PCNA PTMs in the context of replication stress and DNA repair pathways.

Main Results:

  • PCNA PTMs, primarily ubiquitination and SUMOylation, are critical regulators of DDT.
  • These modifications dictate the recruitment and activity of specialized polymerases and repair factors.
  • PCNA PTMs modulate the balance between error-prone TLS and error-free TS pathways.

Conclusions:

  • PCNA PTMs are central to coordinating cellular responses to replication stress.
  • Dysregulation of PCNA PTMs can lead to genomic instability and disease.
  • Understanding PCNA PTMs offers insights into DNA repair, recombination, and mutation processes.
Keywords:
DNA damage tolerancePCNAreplication stresstemplate switchingtranslesion synthesisubiquitination

More Related Videos

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations10:26

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Published on: November 7, 2019

6.1K
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

4.1K

Related Concept Videos

Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
611
Translesion DNA Polymerases02:10

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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...
11.2K
Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
7.7K
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.7K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.6K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.1K