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Provedor de dados:  Genet. Mol. Biol.
País:  Brazil
Título:  Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures
Autores:  Poplawski,Tomasz
Pastwa,Elzbieta
Blasiak,Janusz
Data:  2010-01-01
Ano:  2010
Palavras-chave:  DNA repair
Non-homologous DNA end joining
DNA double-strand breaks
Complementary and non-complementary DNA ends
Resumo:  DNA double-strand breaks (DSBs) are a serious threat to the cell, for if not or miss-repaired, they can lead to chromosomal aberration, mutation and cancer. DSBs in human cells are repaired via non-homologous DNA end joining (NHEJ) and homologous recombination repair pathways. In the former process, the structure of DNA termini plays an important role, as does the genetic constitution of the cells, through being different in normal and pathological cells. In order to investigate the dependence of NHEJ on DSB structure in normal and cancer cells, we used linearized plasmids with various, complementary or non-complementary, single-stranded or blunt DNA termini, as well as whole-cell extract isolated from normal human lymphocytes, chronic myeloid leukemia K562 cells and lung cancer A549 cells. We observed a pronounced variability in the efficacy of NHEJ reaction depending on the type of ends. Plasmids with complementary and blunt termini were more efficiently repaired than the substrate with 3' protruding single-strand ends. The hierarchy of the effectiveness of NHEJ was on average, from the most effective to the least, A549/ normal lymphocytes/ K562. Our results suggest that the genetic constitution of the cells together with the substrate terminal structure may contribute to the efficacy of the NHEJ reaction. This should be taken into account on considering its applicability in cancer chemo-or radiotherapy by pharmacologically modulating NHEJ cellular responses.
Tipo:  Info:eu-repo/semantics/article
Idioma:  Inglês
Identificador:  http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000200027
Editor:  Sociedade Brasileira de Genética
Relação:  10.1590/S1415-47572010005000018
Formato:  text/html
Fonte:  Genetics and Molecular Biology v.33 n.2 2010
Direitos:  info:eu-repo/semantics/openAccess
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