An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination
|Huertas Sánchez, Pablo
García Rubio, María Luisa
Wellinger, Ralf Erik
Luna Varo, Rosa María
Aguilera López, Andrés
|Universidad de Sevilla. Departamento de Genética
|THO/TREX, a conserved eukaryotic protein complex, is a key player at the interface between transcription
and mRNP metabolism. The lack of a functional THO complex impairs transcription, leads to transcriptiondependent
THO/TREX, a conserved eukaryotic protein complex, is a key player at the interface between transcription and mRNP metabolism. The lack of a functional THO complex impairs transcription, leads to transcriptiondependent hyperrecombination, causes mRNA export defects and fast mRNA decay, and retards replication fork progression in a transcription-dependent manner. To get more insight into the interconnection between mRNP biogenesis and genomic instability, we searched for HPR1 mutations that differentially affect gene expression and recombination. We isolated mutants that were barely affected in gene expression but exhibited a hyperrecombination phenotype. In addition, we isolated a mutant, hpr1-101, with a strong defect in transcription, as observed for lacZ, and a general defect in mRNA export that did not display a relevant hyperrecombination phenotype. In THO single-null mutants, but not in the hpr1 point mutants studied, THO and its subunits were unstable. Interestingly, in contrast to hyperrecombinant null mutants, hpr1-101 did not cause retardation of replication fork progression. Transcription and mRNP biogenesis can therefore be impaired by THO/TREX dysfunction without increasing recombination, suggesting that it is possible to separate the mechanism(s) responsible for mRNA biogenesis defects from the further step of triggering transcriptiondependent recombination.
|Ministerio de Educación y Ciencia (MEC). España
Junta de Andalucía
|Huertas Sánchez, P., García Rubio, M.L., Wellinger, R.E., Luna Varo, R.M. y Aguilera López, A. (2006). An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination. Molecular and Cellular Biology, 26 (20), 7451-7465.