|ZFIN ID: ZDB-PUB-210131-4|
Tdp1 protects from topoisomerase 1-mediated chromosomal breaks in adult zebrafish but is dispensable during larval development
Zaksauskaite, R., Thomas, R.C., van Eeden, F., El-Khamisy, S.F.
|Source:||Science advances 7(5): (Journal)|
|Registered Authors:||Thomas, Ruth C., van Eeden, Freek|
|PubMed:||33514542 Full text @ Sci Adv|
Zaksauskaite, R., Thomas, R.C., van Eeden, F., El-Khamisy, S.F. (2021) Tdp1 protects from topoisomerase 1-mediated chromosomal breaks in adult zebrafish but is dispensable during larval development. Science advances. 7(5):.
ABSTRACTDeficiency in the DNA end-processing enzyme, tyrosyl-DNA phosphodiesterase 1 (TDP1), causes progressive neurodegeneration in humans. Here, we generated a tdp1 knockout zebrafish and confirmed the lack of TDP1 activity. In adulthood, homozygotes exhibit hypersensitivity to topoisomerase 1 (Top1) poisons and a very mild locomotion defect. Unexpectedly, embryonic tdp1-/- zebrafish were not hypersensitive to Top1 poisons and did not exhibit increased Top1-DNA breaks. This is in contrast to the hypersensitivity of Tdp1-deficient vertebrate models reported to date. Tdp1 is dispensable in the zebrafish embryo with transcript levels down-regulated in response to Top1-DNA damage. In contrast, apex2 and ercc4 (xpf) transcripts were up-regulated. These findings identify the tdp1-/- zebrafish embryo as the first vertebrate model that does not require Tdp1 to protect from Top1-DNA damage and identify apex2 and ercc4 (xpf) as putative players fulfilling this role. It highlights the requirement of distinct DNA repair factors across the life span of vertebrates.