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Updated: Aug 9, 2026
07:27
Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
Published on: April 29, 2010
Replication fork progression is impaired by transcription in hyperrecombinant yeast cells lacking a functional THO
Ralf E Wellinger1, Félix Prado, Andrés Aguilera
1Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Avda. Reina Mercedes 6, 41012 Seville, Spain.
Molecular and Cellular Biology
|April 4, 2006
Summary
Defective THO/TREX complex function impairs DNA replication fork progression, leading to increased transcription-associated recombination (TAR). This links inefficient messenger ribonucleoprotein (mRNP) biogenesis to genetic instability.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The THO/TREX complex is crucial for transcription and messenger ribonucleoprotein (mRNP) metabolism in eukaryotes.
- THO mutations disrupt transcription and elevate transcription-associated recombination (TAR), but the underlying mechanism remains unclear.
Purpose of the Study:
- To investigate the molecular mechanism linking impaired mRNP biogenesis in THO/TREX mutants to recombination.
- To determine if defects in mRNP biogenesis affect DNA replication.
Main Methods:
- Analysis of replication fork progression in hpr1Delta mutants.
- Assessment of TAR events during different cell cycle phases (S and G2).
- Evaluation of Rad52 repair foci in budding cells.
Main Results:
- Deficient mRNP biogenesis in hpr1Delta mutants causes replication fork slowdown or pausing, dependent on specific DNA sequences.
- Replication fork progression can be partially rescued by cleaving nascent mRNA.
- hpr1Delta mutants exhibit increased S-phase TAR events and Rad52 foci.
Conclusions:
- Impaired replication fork progression is a key factor in transcription-dependent genomic instability observed in THO mutants.
- Inefficient mRNP biogenesis contributes to genetic instability through replication defects.
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