Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures
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,...
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| Format: | Article |
| Language: | English |
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Sociedade Brasileira de Genética
2010-01-01
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| Series: | Genetics and Molecular Biology |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000200027 |
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| author | Tomasz Poplawski Elzbieta Pastwa Janusz Blasiak |
| author_facet | Tomasz Poplawski Elzbieta Pastwa Janusz Blasiak |
| author_sort | Tomasz Poplawski |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T06:42:08Z |
| format | Article |
| id | doaj.art-7f85483ddede4fdf84d0da7718eefe4f |
| institution | Directory Open Access Journal |
| issn | 1415-4757 1678-4685 |
| language | English |
| last_indexed | 2024-12-23T06:42:08Z |
| publishDate | 2010-01-01 |
| publisher | Sociedade Brasileira de Genética |
| record_format | Article |
| series | Genetics and Molecular Biology |
| spelling | doaj.art-7f85483ddede4fdf84d0da7718eefe4f2022-12-21T17:56:41ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1415-47571678-46852010-01-01332368373Non-homologous DNA end joining in normal and cancer cells and its dependence on break structuresTomasz PoplawskiElzbieta PastwaJanusz BlasiakDNA 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000200027DNA repairnon-homologous DNA end joiningDNA double-strand breakscomplementary and non-complementary DNA ends |
| spellingShingle | Tomasz Poplawski Elzbieta Pastwa Janusz Blasiak Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures Genetics and Molecular Biology DNA repair non-homologous DNA end joining DNA double-strand breaks complementary and non-complementary DNA ends |
| title | Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures |
| title_full | Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures |
| title_fullStr | Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures |
| title_full_unstemmed | Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures |
| title_short | Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures |
| title_sort | non homologous dna end joining in normal and cancer cells and its dependence on break structures |
| topic | DNA repair non-homologous DNA end joining DNA double-strand breaks complementary and non-complementary DNA ends |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000200027 |
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