Ionising radiation‐ (IR‐) induced DNA double‐strand breaks (DSBs) are considered to be the deleterious DNA lesions that pose a serious threat to genomic stability. The major DNA repair pathways, including classical nonhomologous end joining, homologous recombination, single‐strand annealing, and alternative end joining, play critical roles in countering and eliciting IR‐induced DSBs to ensure genome integrity. If the IR‐induced DNA DSBs are not repaired correctly, the residual or incorrectly repaired DSBs can result in genomic instability that is associated with certain human diseases. Although many efforts have been made in investigating the major mechanisms of IR‐induced DNA DSB repair, it is still unclear what determines the choices of IR‐induced DNA DSB repair pathways. In this review, we discuss how the mechanisms of IR‐induced DSB repair pathway choices can operate in irradiated cells. We first briefly describe the main mechanisms of the major DNA DSB repair pathways and the related key repair proteins. Based on our understanding of the characteristics of IR‐induced DNA DSBs and the regulatory mechanisms of DSB repair pathways in irradiated cells and recent advances in this field, We then highlight the main factors and associated challenges to determine the IR‐induced DSB repair pathway choices. We conclude that the type and distribution of IR‐induced DSBs, chromatin state, DNA‐end structure, and DNA‐end resection are the main determinants of the choice of the IR‐induced DNA DSB repair pathway.

S: Space biological effects are mainly a result of space radiation particles with high linear energy transfer (LET); therefore, accurate measurement of high LET space radiation is vital. The radiation in low Earth orbits is composed mainly of high‐energy galactic cosmic rays (GCRs), solar energetic particles, particles of radiation belts, the South Atlantic Anomaly, and the albedo neutrons and protons scattered from the Earth's atmosphere. CR‐39 plastic nuclear track detectors sensitive to high LET are the best passive detectors to measure space radiation. The LET method that employs CR‐39 can measure all the radiation LET spectra and quantities. CR‐39 detectors can also record the incident directions and coordinates of GCR heavy ions that pass through both CR‐39 and biosamples, and the impact parameter, the distance between the particle's incident point and the seed's spore, can then be determined. The radiation characteristics and impact parameter of GCR heavy ions are especially beneficial for in‐depth research regarding space radiation biological effects. The payload returnable satellite SJ‐10 provided an excellent opportunity to investigate space radiation biological effects with CR‐39 detectors. The space bio‐effects experiment was successfully conducted on board the SJ‐10 satellite. This paper introduces space radiation in low Earth orbits and the LET method in radiation‐related research and presents the results of nuclear tracks and biosamples hitting distributions of GCR heavy ions, the radiation LET spectra, and the quantities measured for the SJ‐10 space mission. The SJ‐10 bio‐experiment indicated that radiation may produce significant bio‐effects.

Transcriptome profiles are sensitive to space stressors and serve as valuable indicators of the biological effects during spaceflight. Herein, we transformed the expression profiles into gene interaction patterns by single-sample networks (SSNs) and performed the integrated analysis on the 301 spaceflight and 290 ground control samples, which were obtained from the GeneLab platform. Specifically, an individual SSN was established for each sample. Based on the topological structures of 591 SSNs, the differentially interacted genes (DIGs) were identified between spaceflights and ground controls. The results showed that spaceflight disrupted the gene interaction patterns in mice and resulted in significant enrichment of biological processes such as protein/amino acid metabolism and nucleic acid (DNA/RNA) metabolism (P-value < 0.05). We observed that the mice exposed to radiation doses within the three intervals (4.66–7.14, 7.592–8.295, 8.49–22.099 mGy) exhibited similar gene interaction patterns. Low and medium doses resulted in changes to the circadian rhythm, while the damaging effects on genetic material became more pronounced in higher doses. The gene interaction patterns in response to space stressors varied among different tissues, with the spleen, lung, and skin being the most responsive to space radiation (P-value < 0.01). The changes observed in gene networks during spaceflight conditions might contribute to the development of various diseases, such as mental disorders, depression, and metabolic disorders, among others. Additionally, organisms activated specific gene networks in response to virus reactivation. We identified several hub genes that were associated with circadian rhythms, suggesting that spaceflight could lead to substantial circadian rhythm dysregulation.

Space radiations and microgravity both could cause DNA damage in cells, but the effects of microgravity on DNA damage response to space radiations are still controversial. A mRNA microarray and microRNA micro- array in dauer larvae of Caenorhabditis elegans (C. elegans) that endured spaceflight environment and space radiations environment during 16.5-day Shenzhou-8 space mission was performed. Twice as many transcripts significantly altered in the spaceflight environment than space radiations alone. The majority of alterations were related to protein amino acid dephosphorylation and histidine metabolic and catabolic processes. From about 900 genes related to DNA damage response, 38 differentially expressed genes were extracted; most of them differentially expressed under spaceflight environment but not space radiations, although the identical directions of alteration were observed in both cases. cel-miR-81, cel- miR-82, cel-miR-124 and cel-miR-795 were predicted to regulate DNA damage response through four different anti-correlated genes. Evidence was provided that, in the presence of space radiations, microgravity probably enhanced the DNA damage response in C. elegans by integrating the transcriptome and microRNome.

To identify sensitive genes for space radiation, we integrated the transcriptomic samples of spaceflight mice from GeneLab and predicted the radiation doses absorbed by individuals in space. A single-sample network (SSN) for each individual sample was constructed. Then, using machine learning and genetic algorithms, we built the regression models to predict the absorbed dose equivalent based on the topological structure of SSNs. Moreover, we analyzed the SSNs from each tissue and compared the similarities and differences among them. Our model exhibited excellent performance with the following metrics: R2=0.980, MSE=6.74e-04, and the Pearson correlation coefficient of 0.990 (p value <.0001) between predicted and actual values. We identified 20 key genes, the majority of which had been proven to be associated with radiation. However, we uniquely established them as space radiation sensitive genes for the first time. Through further analysis of the SSNs, we discovered that the different tissues exhibited distinct mechanisms in response to space stressors. The topology structures of SSNs effectively predicted radiation doses under spaceflight conditions, and the SSNs revealed the gene regulatory patterns within the organisms under space stressors.