Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice

Gemma Bellí1, Neus Colomina1, Laia Castells-Roca1

  • 1Departament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida, Universitat de Lleida, 25198 Lleida, Spain.

Insights

Proliferating cell nuclear antigen (PCNA) modifications regulate DNA damage tolerance pathways. Understanding PCNA

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Proliferating cell nuclear antigen (PCNA) is a homotrimer crucial for DNA replication.
  • Cells face constant DNA damage, necessitating accurate genome replication.
  • Post-translational modifications of PCNA are key to DNA damage tolerance (DDT) and repair.

Purpose of the Study:

  • To summarize PCNA-related DDT and repair mechanisms in *Saccharomyces cerevisiae*.
  • To explore the role of PCNA modifications in maintaining genome stability and cell survival.
  • To compare fungal PCNA sequences and identify potential antifungal drug targets.

Main Methods:

  • Review of existing literature on PCNA function and modifications.
  • Analysis of PCNA ubiquitination and sumoylation pathways.
  • Comparative sequence analysis of PCNA from fungal pathogens.

Main Results:

  • PCNA ubiquitination drives error-prone translesion synthesis (TLS) or error-free template switching (TS).
  • PCNA sumoylation inhibits homologous recombination-mediated salvage recombination (SR).
  • PCNA structural features and epitopes in fungal pathogens were identified.

Conclusions:

  • PCNA modifications are critical for coordinating DNA repair and tolerance, ensuring genome stability.
  • PCNA's role in fork protection during replication stress requires further investigation.
  • Fungal PCNA epitopes represent potential targets for novel antifungal therapies.

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

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...
9.3K
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...
10.1K
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....
7.0K
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
31.5K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
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...
3.8K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.7K