Abstract

DNA polymerase µ is involved in DNA repair, V(D)J recombination and likely somatic hypermutation of immunoglobulin genes. Our previous studies demonstrated that spaceflight conditions affect immunoglobulin gene expression and somatic hypermutation frequency. Consequently, we questioned whether Polμ expression could also be affected. To address this question, we characterized Polμ of the Iberian ribbed newt Pleurodeles waltl and exposed embryos of that species to spaceflight conditions or to environmental modifications corresponding to those encountered in the International Space Station. We noted a robust expression of Polμ mRNA during early ontogenesis and in the testis, suggesting that Polμ is involved in genomic stability. Full-length Polμ transcripts are 8–9 times more abundant in P. waltl than in humans and mice, thereby providing an explanation for the somatic hypermutation predilection of G and C bases in amphibians. Polμ transcription decreases after 10 days of development in space and radiation seem primarily involved in this down-regulation. However, space radiation, alone or in combination with a perturbation of the circadian rhythm, did not affect Polμ protein levels and did not induce protein oxidation, showing the limited impact of radiation encountered during a 10-day stay in the International Space Station.

Highlights

  • The immune system is affected by environmental changes encountered during spaceflight such as confinement, microgravity, biomechanical stresses, radiation and disruption of the circadian rhythm

  • These primers allowed the amplification of two products that presented strong homologies with the corresponding regions of human, mouse, Xenopus and zebrafish Polm mRNAs

  • Overexpression of Full-length Polm mRNA in P. waltl In this study, we report the first sequencing of Polm in a urodele amphibian

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Summary

Introduction

The immune system is affected by environmental changes encountered during spaceflight such as confinement, microgravity, biomechanical stresses, radiation and disruption of the circadian rhythm. To improve our knowledge concerning the effects of spaceflight on humoral immunity, we used the Iberian ribbed newt Pleurodeles waltl as animal model. This amphibian species is a good model for studies applicable for human health because it was shown that the cardinal elements of the adaptive immune system are shared by all gnathostomes [3]. This observation was confirmed in P. waltl. Several immunologically important genes and transcripts, such as those encoding AID, Ikaros and the C3 complement component, were shown to be conserved in P. waltl and have expression patterns similar to those observed in mammals ([6,7] and unpublished data)

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