Impairment of replication fork progression mediates RNA polII transcription-associated recombination

• Published in: The EMBO journal Vol. 24; no. 6; pp. 1267 - 1276
• Main Authors: Prado, Félix, Aguilera, Andrés
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 23.03.2005; Blackwell Publishing Ltd
• Subjects: DNA Helicases - genetics; DNA Helicases - physiology; DNA Replication - physiology; genetic instability; Genomic Instability - physiology; homologous recombination; Recombination, Genetic - physiology; Repetitive Sequences, Nucleic Acid - genetics; Repetitive Sequences, Nucleic Acid - physiology; replication; Replication Origin - genetics; Replication Origin - physiology; RNA Polymerase II - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - physiology; transcription; Transcription, Genetic - physiology
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600602

Homologous recombination safeguards genome integrity, but it can also cause genome instability of important consequences for cell proliferation and organism development. Transcription induces recombination, as shown in prokaryotes and eukaryotes for both spontaneous and developmentally regulated events such as those responsible for immunoglobulin class switching. Deciphering the molecular basis of transcription‐associated recombination (TAR) is important in understanding genome instability. Using novel plasmid‐borne recombination constructs in Saccharomyces cerevisiae, we show that RNA polymerase II (RNAPII) transcription induces recombination by impairing replication fork progression. RNAPII transcription concomitant to head‐on oncoming replication causes a replication fork pause (RFP) that is linked to a significant increase in recombination. However, transcription that is codirectional with replication has little effect on replication fork progression and recombination. Transcription occurring in the absence of replication does not affect either recombination or replication fork progression. The Rrm3 helicase, which is required for replication fork progression through nucleoprotein complexes, facilitates replication through the transcription‐dependent RFP site and reduces recombination. Therefore, our work provides evidence that one mechanism responsible for TAR is RNAP‐mediated replication impairment.