Changes in repair pathways of radiation-induced DNA double-strand breaks at the midblastula transition in Xenopus embryo

Author:

Morozumi Ryosuke12,Shimizu Naoto3,Tamura Kouhei3,Nakamura Makoto245,Suzuki Atsushi2,Ishiniwa Hiroko6,Ide Hiroshi3,Tsuda Masataka137

Affiliation:

1. Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University , Higashi-Hiroshima, 739-8526 , Japan

2. Amphibian Research Center, Graduate School of Integrated Sciences for Life, Hiroshima University , Higashi-Hiroshima, 739-8526 , Japan

3. Program of Mathematical and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University , Higashi-Hiroshima, 739-8526 , Japan

4. Department of Physiology, Cardiovascular Research Institute, University of California, San Francisco , San Francisco, CA 94158 , USA

5. Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco , San Francisco, CA 94158 , USA

6. Institute of Environmental Radioactivity, Fukushima University , Fukushima, 960-1296 , Japan

7. Division of Genetics and Mutagenesis, National Institute of Health Sciences , Kanagawa, 210-9501 , Japan

Abstract

Abstract Ionizing radiation (IR) causes DNA damage, particularly DNA double-strand breaks (DSBs), which have significant implications for genome stability. The major pathways of repairing DSBs are homologous recombination (HR) and nonhomologous end joining (NHEJ). However, the repair mechanism of IR-induced DSBs in embryos is not well understood, despite extensive research in somatic cells. The externally developing aquatic organism, Xenopus tropicalis, serves as a valuable model for studying embryo development. A significant increase in zygotic transcription occurs at the midblastula transition (MBT), resulting in a longer cell cycle and asynchronous cell divisions. This study examines the impact of X-ray irradiation on Xenopus embryos before and after the MBT. The findings reveal a heightened X-ray sensitivity in embryos prior to the MBT, indicating a distinct shift in the DNA repair pathway during embryo development. Importantly, we show a transition in the dominant DSB repair pathway from NHEJ to HR before and after the MBT. These results suggest that the MBT plays a crucial role in altering DSB repair mechanisms, thereby influencing the IR sensitivity of developing embryos.

Funder

Institute of Environmental Radioactivity

Fukushima University

JSPS KAKENHI

KOSE Cosmetology Research Foundation

Takahashi Industrial and Economic Research Foundation

Hoansha Foundation

Program of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science

Publisher

Oxford University Press (OUP)

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