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DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens

BACKGROUND: The maintenance of genomic integrity is the responsibility of a complex network, denominated the DNA damage response (DDR), which controls the lesion detection and DNA repair. The main repair pathways are base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR)...

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Autores principales: Mota, Maria Beatriz S., Carvalho, Marcelo Alex, Monteiro, Alvaro N. A., Mesquita, Rafael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849265/
https://www.ncbi.nlm.nih.gov/pubmed/31711518
http://dx.doi.org/10.1186/s13071-019-3792-1
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author Mota, Maria Beatriz S.
Carvalho, Marcelo Alex
Monteiro, Alvaro N. A.
Mesquita, Rafael D.
author_facet Mota, Maria Beatriz S.
Carvalho, Marcelo Alex
Monteiro, Alvaro N. A.
Mesquita, Rafael D.
author_sort Mota, Maria Beatriz S.
collection PubMed
description BACKGROUND: The maintenance of genomic integrity is the responsibility of a complex network, denominated the DNA damage response (DDR), which controls the lesion detection and DNA repair. The main repair pathways are base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination repair (HR) and non-homologous end joining repair (NHEJ). They correct double-strand breaks (DSB), single-strand breaks, mismatches and others, or when the damage is quite extensive and repair insufficient, apoptosis is activated. METHODS: In this study we used the BLAST reciprocal best-hit methodology to search for DDR orthologs proteins in Aedes aegypti. We also provided a comparison between Ae. aegypti, D. melanogaster and human DDR network. RESULTS: Our analysis revealed the presence of ATR and ATM signaling, including the H2AX ortholog, in Ae. aegypti. Key DDR proteins (orthologs to RAD51, Ku and MRN complexes, XP-components, MutS and MutL) were also identified in this insect. Other proteins were not identified in both Ae. aegypti and D. melanogaster, including BRCA1 and its partners from BRCA1-A complex, TP53BP1, PALB2, POLk, CSA, CSB and POLβ. In humans, their absence affects DSB signaling, HR and sub-pathways of NER and BER. Seven orthologs not known in D. melanogaster were found in Ae. aegypti (RNF168, RIF1, WRN, RAD54B, RMI1, DNAPKcs, ARTEMIS). CONCLUSIONS: The presence of key DDR proteins in Ae. aegypti suggests that the main DDR pathways are functional in this insect, and the identification of proteins not known in D. melanogaster can help fill gaps in the DDR network. The mapping of the DDR network in Ae. aegypti can support mosquito biology studies and inform genetic manipulation approaches applied to this vector.
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spelling pubmed-68492652019-11-15 DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens Mota, Maria Beatriz S. Carvalho, Marcelo Alex Monteiro, Alvaro N. A. Mesquita, Rafael D. Parasit Vectors Review BACKGROUND: The maintenance of genomic integrity is the responsibility of a complex network, denominated the DNA damage response (DDR), which controls the lesion detection and DNA repair. The main repair pathways are base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination repair (HR) and non-homologous end joining repair (NHEJ). They correct double-strand breaks (DSB), single-strand breaks, mismatches and others, or when the damage is quite extensive and repair insufficient, apoptosis is activated. METHODS: In this study we used the BLAST reciprocal best-hit methodology to search for DDR orthologs proteins in Aedes aegypti. We also provided a comparison between Ae. aegypti, D. melanogaster and human DDR network. RESULTS: Our analysis revealed the presence of ATR and ATM signaling, including the H2AX ortholog, in Ae. aegypti. Key DDR proteins (orthologs to RAD51, Ku and MRN complexes, XP-components, MutS and MutL) were also identified in this insect. Other proteins were not identified in both Ae. aegypti and D. melanogaster, including BRCA1 and its partners from BRCA1-A complex, TP53BP1, PALB2, POLk, CSA, CSB and POLβ. In humans, their absence affects DSB signaling, HR and sub-pathways of NER and BER. Seven orthologs not known in D. melanogaster were found in Ae. aegypti (RNF168, RIF1, WRN, RAD54B, RMI1, DNAPKcs, ARTEMIS). CONCLUSIONS: The presence of key DDR proteins in Ae. aegypti suggests that the main DDR pathways are functional in this insect, and the identification of proteins not known in D. melanogaster can help fill gaps in the DDR network. The mapping of the DDR network in Ae. aegypti can support mosquito biology studies and inform genetic manipulation approaches applied to this vector. BioMed Central 2019-11-11 /pmc/articles/PMC6849265/ /pubmed/31711518 http://dx.doi.org/10.1186/s13071-019-3792-1 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Mota, Maria Beatriz S.
Carvalho, Marcelo Alex
Monteiro, Alvaro N. A.
Mesquita, Rafael D.
DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens
title DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens
title_full DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens
title_fullStr DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens
title_full_unstemmed DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens
title_short DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens
title_sort dna damage response and repair in perspective: aedes aegypti, drosophila melanogaster and homo sapiens
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849265/
https://www.ncbi.nlm.nih.gov/pubmed/31711518
http://dx.doi.org/10.1186/s13071-019-3792-1
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