Modulation of Pleurodeles waltl DNA Polymerase mu Expression by Extreme Conditions Encountered during Spaceflight

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.

Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice

“…An assessment of the impact of hypergravity on the similarly assembled T cell receptor repertoire of neonatal mice showed low correlation of individual Beta chain V- and J-gene segment recombination frequencies between control animals and animals subjected to centrifugation. 85% of gene V/J-gene segment combinations were not shared among the two treatment groups (Ghislin et al, 2015) and the differences could be attributed to changes in somatic recombination machinery under altered gravity conditions (Schenten et al, 2013, Ghislin et al, 2015).…”

Towards human exploration of space: The THESEUS review series on immunology research priorities

“…61 Amphibians are interesting models for analyzing the effects of spaceflight on the immune system because cardinal elements of the adaptive immune system are shared by all gnathostomes. 1 , 62–69 Later on, adult P. waltl were immunized with protein onboard the Mir space station. The analysis of these animals revealed an increase of IgY heavy chain mRNAs (IgY is the physiological counterpart of human IgA 66 ) in the spleen of flown animals.…”

Transcriptome Analysis by RNA Sequencing of Mouse Embryonic Stem Cells Stocked on International Space Station for 1584 Days in Frozen State after Culture on the Ground

“…Also, transcriptome analysis was carried out on the ground using low-dose irradiation and modeled microgravity showing multiple altered neurological pathways [ 61 ] or a hematological system with transforming growth factor β signaling [ 62 ]. During the flight on the ISS for 10 days, a decrease in the expression of the newt ( Pleurodeles waltl ) gene of DNA repair (Pol mu) was observed due to the space radiation or microgravity [ 63 ]. Comprehensive analyses of transcripts have been carried out on the International Space Station to examine the effects of space radiation and microgravity on animals, and it was found that the expression of several microRNAs in blood might regulate the TGFβ1 gene, which is a master regulator coordinating for a systemic response to microgravity and space radiation [ 64 ].…”