Papel da resposta SOS no reparo de danos induzidos por mitomicina C e na resposta aos antibióticos beta-lactâmicos em Caulobacter crescentus.

Kulishev, Carina Oliveira Lopes

doi:10.11606/D.42.2014.tde-12082014-180126

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Master's Dissertation

DOI

https://doi.org/10.11606/D.42.2014.tde-12082014-180126

Document

Master's Dissertation

Author

Kulishev, Carina Oliveira Lopes (Catálogo USP)

Full name

Carina Oliveira Lopes Kulishev

Institute/School/College

Instituto de Ciências Biomédicas

Knowledge Area

Microbiology

Date of Defense

2014-04-22

Published

São Paulo, 2014

Supervisor

Galhardo, Rodrigo da Silva (Catálogo USP)

Committee

Galhardo, Rodrigo da Silva (President)
Baldini, Regina Lúcia
Costa, Renata Maria Augusto da

Title in Portuguese

Papel da resposta SOS no reparo de danos induzidos por mitomicina C e na resposta aos antibióticos beta-lactâmicos em Caulobacter crescentus.

Keywords in Portuguese

Caulobacter crescentus
Beta-lactâmicos
Mitomicina C
Mutagênese
Resposta SOS

Abstract in Portuguese

O sistema SOS controla a expressão de diversos genes, muitos envolvidos com o reparo de DNA. Caulobacter crescentus vem emergindo como um modelo alternativo interessante para o estudo de mecanismos de reparo de DNA. Temos como objetivos realizar uma análise funcional de genes de função desconhecida regulados por SOS, e investigar a indução de SOS por antibióticos beta-lactâmicos em C. crescentus. Análises funcionais dos genes CC_3424 e CC_3467 mostraram que deleções nestes genes resultam em fenótipo de sensibilidade à mitomicina C (MMC). CC_3424 possui similaridade com glioxalases e CC_3467 com endonucleases. Acreditamos que CC_3467 atue no reparo de ligações intercadeia no DNA, e que CC_3424 atue detoxificando a MMC das células. Estudos dos efeitos biológicos da indução do sistema SOS mostram que a cefalexina (CFE) induz este regulon em concentrações subinibitórias. Células tratadas com CFE apresentam mais danos oxidativos do tipo 8-oxoguanina. Estes resultados mostram que concentrações subinibitórias de CFE resultam em estresse oxidativo em C. crescentus.

Title in English

Role of the SOS response in the repair of damage induced by mitomycin C and in the response to beta-lactams in Caulobacter crescentus.

Keywords in English

Caulobacter crescentus
Beta-lactams
Mitomycin C
Mutagenesis
SOS response

Abstract in English

The SOS response controls the expression of several genes, many of which are involved in DNA repair mechanisms. Caulobacter crescentus has emerged as an alternative bacterial model for DNA repair. As aims, we will undertake a functional analysis of some of the genes regulated by the SOS response, and will investigate the SOS induction by beta-lactam antibiotics in C. crescentus. Functional analysis of the genes CC_3424 and CC_3467 showed that deletions in these genes result in a phenotype of sensitivity to mitomycin C (MMC). CC_3424 has similarity to glyoxalase and CC_3467 to endonucleases. We believe that the CC_3467 gene plays a role in the repair of interstrand crosslinks in the DNA, while CC_3424 acts in MMC cellular detoxification. Studies of biological effects of SOS induction showed that subinibitory concentrations of cephalexin (CFE) induce the SOS regulon. Cells treated with CFE have higher concentrations of 8-oxoG oxidative damage. These results show that subinibitory concentrations of cephalexin leads to cellular oxidative stress in C. crescentus.

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CarinaOliveiraLopesKulishev_Mestrado_I.pdf (3.23 Mbytes)

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Publishing Date

2014-08-14

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