Journal
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
Volume 768, Issue -, Pages 68-77Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrrev.2016.04.004
Keywords
DNA topoisomerases; Topoisomerase II inhibitors; DNA repair; NER
Funding
- FAPERGS (Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul, Porto Alegre, Brazil) [12/1926-9]
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brasilia, Brazil) [479564/2013-2]
- PRONEX-FAPERGS/CNPq [10/0044-3]
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brasilia, Brazil)
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In cancer treatment, chemotherapy is one of the main strategies used. The knowledge of the cellular and molecular characteristics of tumors allows the use of more specific drugs, making the removal of tumors more efficient. Among the drugs of choice in these treatments, topoisomerase inhibitors are widely used against different types of tumors. Topoisomerases are enzymes responsible for maintaining the structure of DNA, altering its topological state temporarily during the processes of replication and transcription, in order to avoid supercoiling and entanglements at the double helix. The DNA damage formed as a result of topoisomerase inhibition can be repaired by DNA repair mechanisms. Thus, DNA repair pathways can modulate the effectiveness of chemotherapy. Homologous recombination (HR) and non-homologous end joining (NHEJ) are the main pathways involved in the removal of double strand breaks (DSBs); while nucleotide excision repair (NER) is mainly characterized by the removal of lesions that lead to significant structural distortions in the DNA double helix. Evidence has shown that DSBs are the main type of damage resulting from the inhibition of the DNA topoisomerase II enzyme, and therefore the involvement of HR and NHEJ pathways in the repair process is well established. However, some topoisomerase II inhibitors induce other types of lesions, like DNA adducts, interstrand crosslinks and reactive oxygen species, and studies have shown that other DNA repair pathways might be participating in removing injury induced by these drugs. This review aims to correlate the involvement of proteins from different DNA repair pathways in response to these drugs, with an emphasis on NER. (C) 2016 Elsevier B.V. All rights reserved.
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