Congratulations to Laura, Beatriz and Manuel, who have all brilliantly defended their BSc theses. Moreover, also kudos to Clara, who after completing her MSc thesis with top marks, will continue in the lab as a PhD student in the Molecular Medicine program.
Today is a special day for the lab. The current issue of Nucleic Acids Research features two papers from the group reflecting the PhD projects of Tomás Lama Díaz and Raquel Carreira Rodríguez.
In Alternative translation initiation by ribosomal leaky scanning produces multiple isoforms of the Pif1 helicase, Tomás wrestled with the complex alternative translation initiation mechanism that enables the generation of mitochondrial and nuclear isoforms of this conserved helicase from the same mRNA. He demonstrated that ribosomal leaky scanning produces not only these, but also novel, previously uncharacterized Pif1 isoforms, with a contribution of both in-frame, downstream AUGs as well as near-cognate start codons. This provides an explanation for long-observed, suboptimal behaviour of the widely employed mitochondrial- (pif1-m1) and nuclear-deficient (pif1-m2) alleles. Importantly, we have taken advantage of this refined model of PIF1 mRNA translation to develop improved mitochondrial- and nuclear-null pif1 mutants, which will serve as valuable tools to elucidate novel functions of this helicase and to disambiguate previously described genetic interactions of PIF1 in the context of nuclear and mitochondrial genome stability. Today is a special day for the lab. The current issue of Nucleic Acids Research features two papers from the group reflecting the PhD projects of Raquel Carreira Rodríguez and Tomás Lama Díaz.
Raquel´s paper, Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors, culminates a long collaboration with the Lumir Krejci´s lab at Masaryk University (Brno, Czech Republic) where she spearheaded the characterization of the activitites of the yeast structure-selective nucleases Mus81-Mms4 and Yen1 on various D-loop substrates. Our biochemical approach demonstrated that both enzymes can cleave this central recombination intermediate. Crucially, we show for the first time that the simultaneous action of Mus81 and Yen1 on a D-loop, followed by ligation, is sufficient to recreate the formation of a half-crossover precursor in vitro. Our results provide a mechanistic explanation for the formation of half-crossovers and chromosomal loss events that is consistent with previous genetic data, highlighting the relevance of the tight regulation of these SSEs to prevent chromosomal rearrangements. We welcome three new members for summer internships in July: Erika Ventoso, from University Rovira i Virgili in Tarragona; Lía Figueiras from USC, who secured one of the 14 CiMUS Summer School fellowships; and Marina Guerrero from Jordi Frigola´s lab at IDIBGI (Girona) for a PhD research stay. We hope you enjoy your time with us!
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