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Scheme representing the different steps of nucleotide excision repair
Scheme representing the different steps of nucleotide excision repair

DNA Repair Lab

Most of our research activities are based on the understanding of DNA repair and mutagenesis mechanisms in living cells. Several of our approaches include studies on mammalian (basically human) cells in culture, where we try to learn the mechanisms of DNA damage tolerance and removal and cell death (apoptosis) signalling in DNA repair deficient cells (most from the human disease xeroderma pigmentosum). We have developed several recombinant viral vectors (mainly derived from adenovirus), carrying DNA repair genes, which are used in these studies. These vectors are also been used directly in vivo, by infecting DNA repair mice strains, making our lab in the trail for Gene Therapy protocols targeted for skin diseases. Recently, we are developing systems to knock-down DNA repair genes with RNA interference in other to investigate the mechanisms of the interaction of different DNA repair processes. With the recent enormous amount of data generated by genomic approaches, and our own work in genome projects, we have approached the analysis of genome evolution, by using bioinformatics tools. In fact, DNA repair genes are highly conserved and highly appropriated for these studies, as indicated by our work with DNA repair genes in plants. Moreover, based on the knowledge of the complete genome sequence of Caulobacter crescentus, we intend to identify and investigate the genes involved in the DNA repair of this alpha proteobacteria. This bacterial model has been highly useful in studies of cell differentiation and cell cycle in prokaryotes and the possibility to synchronize these bacteria may be useful to ascertain the effect of cell cycle on the repair functions in these cells.

Main recent publications complete list:

01. Moraes, MCS, Cabral-Neto, JB, Menck, CFM (2012) DNA repair mechanisms protect our genome from carcinogenesis. Frontiers in Bioscience, 17: 1362-1388.

02. Moraes MC, Andrade AQ, Carvalho H, Guecheva T, Agnoletto MH, Henriques JA, Sarasin A, Stary A, Saffi J, Menck CF (2012) Both XPA and DNA polymerase eta are necessary for the repair of doxorubicin-induced DNA lesions. Cancer Lett. 314: 108-118. (PDF)

03. Schuch AP, Menck CF (2010) The genotoxic effects of DNA lesions induced by artificial UV-radiation and sunlight. J Photochem Photobiol B; 99(3): 111-116.(PDF)

04. Cutiño-Jiménez AM, Martins-Pinheiro M, Lima WC, Martín-Tornet A, Morales OG, Menck CFM (2010) Evolutionary placement of Xanthomonadales based in conserved protein signature sequences. Molecular Phylogenetics and Evolution, 54: 524-534.(PDF)

05. Batista LF, Roos WP, Kaina B and Menck CF (2009) p53 mutant human glioma cells are sensitive to UV-C induced apoptosis due to impaired CPD removal. Molecular Cancer Research 7(2): 237-246.(PDF)

06. Leite, RA, Marchetto, MC, Muotri, AC, Vasconcelos, DM, Oliveira, ZNP, Machado MCR , Menck, CF (2009) Identification of XP complementation groups by recombinant adenovirus carrying DNA repair genes. Journal Investigative Dermatology, 129(2):502-506.(PDF)

07. Lima WC, Varani AM and Menck CF (2009) NAD biosynthesis evolution in bacteria: lateral gene transfer of kynurenine pathway in Xanthomonadales and Flavobacteriales. Molecular Biology of Evolution, 26(2): 399-406.(PDF)

08. Batista LF, Kaina B, Meneghini R, Menck CF (2009) How DNA lesions are turned into powerful killing structures: Insights from UV-induced apoptosis. Mutat Res Reviews, 681(2-3):197-208.(PDF)

09. Lima-Bessa KM, Armelini MG, Chiganças V, Jacysyn JF, Amarantes-Mendes GP, Sarasin A and Menck CFM (2008) CPDs and 6-4PPs play different roles in UV-induced cell death in normal and NER-deficient human cells, DNA Repair 7(2): 303-312.(PDF)

10. Marchetto MCN*, Muotri AR*, Burns DK, Friedberg EC and Menck CFM (2004) Gene transduction in skin cells: preventing cancer in xeroderma pigmentosum mice. Proc. Natl. Acad. Sci. USA 101 (51): 17759-64. Both authors have equally contributed.(PDF)

11. Costa RM, Chiganças V, Galhardo RS, Carvalho H, Menck CFM (2003) The eukaryotic nucleotide excision repair pathway. Biochimie, 85: 1083-1099.(PDF)

12. Menck, CFM (2002) Shining a light on photolyases. Nature Genetics, News and Views, 32: 338-339.(PDF)

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