The DNA damage tolerance factor Rad5 and telomere replication

Stefano Mattarocci1

  • 1Université Paris-Saclay, Université Paris-Cité, CEA, Institut de biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, Inserm, France. stefano.mattarocci@inserm.fr.

Current Genetics
|May 26, 2025
PubMed

Insights

The DNA Damage Tolerance (DDT) pathway uses Rad5 to help replicate DNA past blocks. Rad5 binds to telomeres, suggesting a role in telomere replication and DNA repair.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA replication requires mechanisms to overcome blocks, such as the DNA Damage Tolerance (DDT) pathway.
  • PCNA ubiquitination is central to DDT, mediating error-free or error-prone DNA damage bypass.
  • Rad5 is a key factor in yeast Saccharomyces cerevisiae, influencing both DDT pathways and interacting with telomeres.

Purpose of the Study:

  • To review the current understanding of the link between Rad5 and telomeres.
  • To present evidence for Rad5 binding to yeast telomeres.
  • To explore the functional interplay between telomere replication and DNA damage tolerance.

Main Methods:

  • Literature review of Rad5 function in DNA Damage Tolerance.
  • Experimental evidence demonstrating Rad5 binding to telomeres in Saccharomyces cerevisiae.
  • Analysis of Rad5 enrichment during telomere replication.

Main Results:

  • Rad5 plays a dual role in DDT, promoting error-free bypass via PCNA polyubiquitination and interacting with polymerases for error-prone bypass.
  • Rad5 demonstrates binding to yeast telomeres.
  • Rad5 shows enrichment at telomeres specifically during their replication.

Conclusions:

  • Rad5 is functionally linked to telomeres in yeast.
  • The findings suggest a novel connection between telomere replication and DNA damage tolerance mechanisms.
  • Further research is warranted to elucidate the precise role of Rad5 at telomeres during replication.

Related Concept Videos

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...
11.0K
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...
10.0K
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...
3.0K
Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
26.9K
Telomeres and Telomerase02:41

Telomeres and Telomerase

7.0K
Replication in Eukaryotes01:29

Replication in Eukaryotes

In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
17.1K