Polq-Mediated End Joining Is Essential for Surviving DNA Double-Strand Breaks during Early Zebrafish Development

Summer B Thyme; Alexander F Schier

doi:10.1016/j.celrep.2016.03.072

Polq-Mediated End Joining Is Essential for Surviving DNA Double-Strand Breaks during Early Zebrafish Development

Cell Rep. 2016 Apr 26;15(4):707-714. doi: 10.1016/j.celrep.2016.03.072. Epub 2016 Apr 14.

Authors

Summer B Thyme¹, Alexander F Schier²

Affiliations

¹ Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: sthyme@gmail.com.
² Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; FAS Center for Systems Biology, Harvard University, MA 02138, USA. Electronic address: schier@fas.harvard.edu.

Abstract

Error-prone repair of DNA double-strand breaks (DSBs) has been postulated to occur through classical non-homologous end joining (NHEJ) in systems ranging from nematode somatic tissues to zebrafish embryos. Contrary to this model, we show that zebrafish embryos mutant for DNA polymerase theta (Polq), a critical component of alternative end joining (alt-EJ), cannot repair DSBs induced by CRISPR/Cas9 or ionizing radiation. In the absence of DSBs, polq mutants are phenotypically normal, but they do not survive mutagenesis and display dramatic differences in the mutation profiles compared with the wild-type. These results show that alt-EJ repair is essential and dominant during the early development of a vertebrate.

Abstract

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