Leonardo Carmo de Andrade Lima

I Am a graduate student of Biology at University of Sao Paulo, supported by FAPESP.

Project Abstract

With all the potential that ultraviolet (UV) radiation has to damage DNA, cellular mechanisms have been selected evolutionarily, such as repair and tolerance to DNA damage, besides checkpoint machinery which coordinates cell-cycle progression and maintains genome stability and maintenance. The ATR protein has a central role by coordinating this DNA damage checking signaling. It is activated by single strand breaks and arrested replication forks. These events are normally triggered by UV radiation and results in stalled or halted cell-cycle, which gives time to appropriate lesion repair. The more flexible and versable repair path is the nucleotide excision repair (NER), which recognizes bulky DNA lesions. Cells also possess a mechanism where specialized DNA polymerases help to overcome replication blocks when occasional unrepaired DNA lesions stall the replication machinery, accomplishing a translesion synthesis (TLS). The DNA polymerase η (polη), expressed by XPV gene, has a great significance in this context. Therefore, we intend in this project to apply the RNA interference (RNAi) technology to induce ATR and XPV silencing, in order to obtain information of how human fibroblast cells, mainly deficient in NER, behave after UVB irradiation. To achieve this, we will perform survival and cytometry assays to investigate these cells sensibility.

Publications

1.Andrade-Lima, L. C.; Jogo da Resposta ao Dano no DNA. Revista Genética na Escola. Vol IX, artigo 6. 2014 (http://geneticanaescola.com.br/vol-ix1-artigo-06/)

2. Veloso A, Biewen B, Paulsen MT, Berg N, Carmo de Andrade Lima L, Prasad J, Bedi K, Magnuson B, Wilson TE, Ljungman M.; Genome-wide transcriptional effects of the anti-cancer agent camptothecin. PLoS One. 2013 Oct 23;8(10) (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078190)

3.Kobayashi GS, Alvizi L, Sunaga DY, Francis-West P, Kuta A, Almada BV, Ferreira SG, de Andrade-Lima LC, Bueno DF, Raposo-Amaral CE, Menck CF, Passos-Bueno MR.; Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate. PLoS One. 2013 Jun 12;8(6) (http://dx.plos.org/10.1371/journal.pone.0065677)

4.Maria Berra C, de Oliveira CS, Machado Garcia CC, Reily Rocha CR, Koch Lerner L, de Andrade Lima LC, da Silva Baptista M, Martins Menck CF.; Nucleotide excision repair activity on DNA damage induced by photoactivated methylene blue. Free Radic Biol Med. 2013 Apr 6;61C:343-356 (http://www.sciencedirect.com/science/article/pii/S0891584913001317)