CiMUS PhD defense: Tomás Lama Díaz

New discoveries on the importance of nuclease and helicase regulation in DNA repair

The new CiMUS PhD defense, "Impact of Pif1 translational mechanism on genetic interactions with YEN1^ON  and other DNA repair enzymes ADN" delves into the study of genetic interactions between a permanently active version of the YEN1 nuclease (YEN1^ON) and the absence of key helicases in DNA replication and repair. In particular, it concludes that the elimination of PIF1 in the presence of YEN1^ON results in a drastic decrease in cellular resistance to genotoxic agents, indicating that the non-programmed cleavage by  Yen1 of secondary structures that accumulate in nuclear DNA in the absence of Pif1 is detrimental to cells.  

This work, directed by Miguel González Blanco, has highlighted the crucial role of nucleases and helicases in DNA repair and genomic stability, providing new insights into the importance of these enzymes and their regulation in DNA replication and repair processes.
Tomás Lama, author of the thesis, said: “This research has shown that precise control of Yen1 nuclease activity is important to avoid the generation of DNA breaks in regions with secondary structures such as those that accumulate in the absence of the Pif1 helicase. This highlights the importance of the correct regulation of these evolutionarily highly conserved proteins to prevent DNA damage and maintain cell viability".

Alternative messenger RNA translation

Furthermore, in this PhD thesis, experiments have been carried out to investigate the translational control of the Pif1 helicase. As a result, the molecular mechanism of alternative initiation of translation of its messenger RNA has been refined, discovering a new nuclear isoform of the enzyme and improving the existing segregating alleles to discern between nuclear and mitochondrial functions of Pif1. These findings are key to better understanding the role and regulation of Pif1 in cellular processes.

Tomás Lama Díaz has been the beneficiary of a pre-doctoral contract from the Xunta de Galicia and has carried out a research stay in the laboratory of Dr. Joao Matos, at the Institute of Biochemistry (ETH,  Zürich). 

In the picture, Tomás Lama Díaz (centre) with members of the committee and the thesis director. From left to right Rodrigo Bermejo (CSIC-CIB Margarita Salas), Uli Rass (Univ. Sussex), Pablo Huertas (CABIMER) and Miguel G. Blanco (CiMUS-USC).