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Understanding the DNA damage response in order to achieve desired gene editing outcomes in mosquitoes

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Abstract

Mosquitoes are high-impact disease vectors with the capacity to transmit pathogenic agents that cause diseases such as malaria, yellow fever, chikungunya, and dengue. Continued growth in knowledge of genetic, molecular, and physiological pathways in mosquitoes allows for the development of novel control methods and for the continued optimization of existing ones. The emergence of site-specific nucleases as genomic engineering tools promises to expedite research of crucial biological pathways in these disease vectors. The utilization of these nucleases in a more precise and efficient manner is dependent upon knowledge and manipulation of the DNA repair pathways utilized by the mosquito. While progress has been made in deciphering DNA repair pathways in some model systems, research into the nature of the hierarchy of mosquito DNA repair pathways, as well as in mechanistic differences that may exist, is needed. In this review, we will describe progress in the use of site-specific nucleases in mosquitoes, along with the hierarchy of DNA repair in the context of mosquito chromosomal organization and structure, and how this knowledge may be manipulated to achieve precise chromosomal engineering in mosquitoes.

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Abbreviations

A-NHEJ:

Alternative non-homologous end joining

C-NHEJ:

Classical non-homologous end joining

CRISPR:

Clustered regulatory interspaced short palindromic repeats

DSB:

Double-stranded break

HE:

Homing endonuclease

HDR:

Homology-directed repair

HRMA:

High-resolution melt curve analysis

RIDL:

Release of insects with dominant lethality

SIT:

Sterile insect technique

SSA:

Single-strand annealing

TALEN:

Transcription activator-like effector nuclease

TE:

Transposable element

ZFN:

Zinc finger nuclease

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Acknowledgments

The project described was supported by grants [AI085091, AI099843] from NIAID, and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIAID.

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Correspondence to Zach N. Adelman.

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Responsible Editors: Natalay Kouprina and Vladimir Larionov

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Overcash, J.M., Aryan, A., Myles, K.M. et al. Understanding the DNA damage response in order to achieve desired gene editing outcomes in mosquitoes. Chromosome Res 23, 31–42 (2015). https://doi.org/10.1007/s10577-014-9450-8

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  • DOI: https://doi.org/10.1007/s10577-014-9450-8

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