Mitochondrial plasticity and replication

Home departments Molecular Biology Mitochondrial plasticity and replication

Research areas:

      -Proteins and substances suppressing Topoisomerase mediated DNA damage.
      -Proteomics of replicative aging.

 Proteins and substances suppressing Topoisomerase mediated DNA damage.

Chemotherapy is an important approach in the treatment of human cancer. Most of the frontline anti-cancer agents are known to interact with DNA or DNA interacting proteins in order to exert their anti-cancer effects. Topoisomerases are enzymes that change the supercoiling of the DNA and are required during transcription, recombination and replication. Topoisomerase inhibitors have recently been introduced in the clinical treatment of solid tumors including colon, lung and ovarian carcinomas.

Little is known about proteins or substances capable of suppressing DNA damage resulting from nicked DNA containing a TopI-DNA complex. Such knowledge has important impacts. The targeted inactivation of proteins that mediate resistance to TopI damage could lead to a more effective treatment of cancer cells. On the other hand the targeted activation of such proteins could result in a local suppression of unwanted side effects observed during drug treatment including hair loss or diarrhoea.


Proteomics of replicative aging.

It is possible to analyse replicative and chronological life-span of single yeast cells, however, a proteomic analysis of 'young' and 'old' yeast requires a technique to enrich for cells having the same replicative age. We currently develop a technique to enrich for sufficient cells with a defined number of cell divisions. Consequently, we want to use a proteomic approach to determine differences between 'young' and 'old' yeast cells at the level of protein content and modifications.


Selected Publications:

de la Loza MC, Gallardo M, García-Rubio M, Izquierdo A, Herrero E, Aguilera A and Wellinger RE. Zim17/Tim15 Links Mitochondrial Iron-Sulfur Cluster Biosynthesis to Nuclear Genome Stability, 2011. Nucleic Acids Res. (ahead of print)

Stuckey R,  Díaz de la Loza MC and Wellinger RE. Cellular responses to mitochondrial DNA damage in yeast. In: Mitochondria: Structure, Functions and Dysfunctions; Pp: 709-729, Ed. Ed. O. Svensson, Nova Science Publishers NY; ISBN 978-1-61761-490-3 (2010)

Gaillard H., Wellinger R.E., Aguilera A. Methods to study transcription-coupled repair in chromatin, 2009. Methods Mol Biol. 523:141-59.

de la Loza MC, Wellinger RE*, Aguilera A. Stimulation of direct-repeat recombination by RNA polymerase III transcription, 2009. DNA Repair (Amst). 8(5):620-6. (*corresponding author)

de la Loza MC, Wellinger RE. A novel approach for organelle-specific DNA damage targeting reveals different susceptibility of mitochondrial DNA to the anticancer drugs camptothecin and topotecan, 2009. Nucleic Acids Res. 37(4):e26.

Gaillard H., Wellinger, R. E. and A. Aguilera. A new connection between mRNA biogenesis and export with transcription-coupled repair, 2007. Nucleic Acids Res; 35(12):3893-906.

Fitzgerald DJ, Schaffitzel C, Berger P, Wellinger R, Bieniossek C, Richmond TJ and I. Berger I. Multiprotein expression strategy for structural biology of eukaryotic complexes, 2007. Structure. 15:275-9

Huertas P., Garcia-Rubio, M. L., Wellinger, R. E., Luna R. and A. Aguilera. A hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination, 2006. Mol. Cell. Biol. 26:7451-65

Wellinger, R. E., Prado F. and A. Aguilera. Replication fork progression is impaired by transcription in yeast cells lacking a functional THO-complex, 2006. Mol. Cell. Biol. 26:3327-3334

Wellinger, R. E., and J. M. Sogo. Rad52-independent accumulation of joint circular minichromosomes during S phase in Saccharomyces cerevisiae, 2003. Mol. Cell. Biol. 23:6363-72

Gonzalez-Barrera, S., F. Cortes-Ledesma, R. E. Wellinger, and A. Aguilera. Equal sister chromatide exchange is a major mechanism of double-strand break repair in yeast, 2003. Mol Cell 11:1661-71

Lucchini, R., R.E. Wellinger, and J. M. Sogo. Nucleosome positioning at the replication fork, 2001. EMBO J 20:7294-302