Abstract
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.
DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion