Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Translesion synthesis (TLS) polymerases are not essential for animal life but prevent genomic scars. This DNA repair pathway ensures genetic information preservation by suppressing DNA double-strand breaks.
Area Of Science
- Molecular Biology
- Genetics
- Genomics
Background
- DNA damage poses a significant threat to genome integrity during replication.
- Translesion synthesis (TLS) polymerases are crucial for bypassing DNA lesions, preventing replication fork collapse and cell death.
Purpose Of The Study
- To investigate the role of TLS in maintaining long-term genome stability in a whole animal model.
- To determine the contribution of Y-family polymerases (REV1, REV3, POLH1, POLK) to preventing mutations and genomic instability.
Main Methods
- Comparative analysis of mutation accumulation in TLS-deficient C. elegans strains.
- Whole genome sequencing to identify mutation types and locations.
- Assessment of genetic redundancies among TLS polymerases.
Main Results
- Animals deficient in all Y-family polymerases or lacking all TLS activity are viable, indicating TLS is not essential for survival.
- TLS deficiency leads to the accumulation of genomic scars, primarily resulting from polymerase theta-mediated end joining (TMEJ).
- These scars are enriched at guanine bases, suggesting TLS suppresses DNA double-strand breaks at guanine adducts.
Conclusions
- TLS activity is vital for preventing the accumulation of detrimental genomic alterations, even in the absence of external genotoxic stress.
- TLS acts in an error-free and anti-clastogenic manner to preserve genetic information by suppressing DNA double-strand breaks.
- The study highlights the critical role of TLS in maintaining genome stability throughout an organism's lifespan.
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
Related Concept Videos
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...
Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore, it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase...
Overview
Synthesis of new DNA molecules starts when DNA polymerase links nucleotides together in a sequence that is complementary to the template DNA strand. DNA polymerase has a higher affinity for the correct base to ensure fidelity in DNA replication. The DNA polymerase furthermore proofreads during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors during Replication Are Corrected by the DNA Polymerase Enzyme
Genomic DNA is...
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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...
Overview
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 fill 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...