Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “space mutagenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

9 recordsLinked to original sources
PubMed2026

Genetic Analysis of Genomic and Methylomic Variation and Identification of Multi-Trait Mutants in Rice Carried on Chang'e-5.

Global food security is facing challenges from population growth to diminishing arable land. Space mutation breeding holds promise for overcoming the variation limitations in conventional breeding; however, the mutagenic effects of the deep-space environment on rice and the transgenerational inheritance patterns of induced variations remain unclear. In this study, rice seeds carried by the Chang'e-5 spacecraft were used as materials. Whole-genome sequencing and whole-genome bisulfite sequencing were performed on the first (SP1) and second generations (SP2) of space-mutagenized plants after their return to Earth. The results showed that the number of genomic variants in the SP2 generation increased significantly compared with SP1, and SNPs, homozygous sites, and variants in coding regions were more heritable. The genome-wide methylation level was elevated in the SP2 generation, and among differentially methylated cytosines, those in the CG context exhibited the highest heritability. Furthermore, large-scale screening for nitrogen efficiency, tolerance to PEG-induced stress, and germination-stage cold resistant mutants was conducted in the SP2 generation, and phenotypic validation was performed in the third generation (SP3). By integrating multi-omics analyses of representative mutants to mine candidate genes, a number of heritable elite mutants were obtained, and seven candidate genes for key traits were identified. This study systematically elucidates the transgenerational inheritance patterns of deep-space-induced variation in rice. The multi-trait mutants obtained provide valuable germplasm resources for gene cloning and breeding applications in rice.

DNA methylation↗
PubMed1976

Misrepair of overlapping daughter strand gaps as a possible mechanism for UV induced mutagenesis in UVR strains of Escherichia coli: a general model for induced mutagenesis by misrepair (SOS repair) of closely spaced DNA lesions.

It has been previously reported that an inducible form of post-replication repair appeared to be required for UV induced mutagenesis in a uvrA strain of Escherichia coli. It is shown here that the numbers of daughter strand gaps requiring inducible repair were similar to the numbers calculated to be overlapping one another in opposite daughter chromosomes. An estimation of survival with no repair of these gaps resembled the survival predicted with no mutagenesis. It is the thus proposed that inducible post-replication repair causes mutagenesis by the repair of overlapping daughter strand gaps. A general model for induced mutagenesis is presented. It is proposed that (a) some DNA lesions introduced by any DNA damaging agent may be close enough to interfere with constitutive repair replication of each other, (b) these lesions induce a repair system (SOS repair) which involves the recA+ lexA+ and polC+ genes (c) repair and concomitant mutagenesis occurs during repair replication by the insertion of mismatched bases opposite the noncoding DNA lesions.

Cell Survival↗
PubMed2026

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis↗
PubMed2026

MRE11 suppresses germline mutagenesis at meiotic double-strand breaks in mice.

SPO11 forms hundreds of double-strand breaks (DSBs) to initiate meiotic recombination that is normally error-free. However, SPO11 activity can be mutagenic when one chromatid incurs closely spaced DSBs (double cuts), especially when DSBs are dysregulated by loss of the ATM kinase. De novo indels and structural variants can arise via end joining at double cuts within a single hotspot (microdeletions) or at adjacent hotspots separated by at least 30 kb, as we now show, sometimes accompanied by ectopic insertions of double-cut fragments. Here, we investigate how meiotic DSB end processing influences end joining. In MRE11-deficient mouse spermatocytes, which do not resect their DSBs, deletions at double cuts occur readily, with end-joining breakpoint profiles closely matching SPO11 DSB profiles. Microdeletions suggest that two DSBs can be as close as ∼21 bp. The tyrosyl-DNA phosphodiesterase TDP2 contributes to both deletion formation and ectopic insertion of double-cut fragments, presumably by removing SPO11 from DNA ends prior to joining. Finally, observations suggest a cooperative role for MRE11 and ATM in locally regulating DSB distributions. Our findings provide insight into the mechanism of de novo mutation origin, emphasizing the role of meiotic DSBs in shaping genome evolution.

Animals↗
PubMed2026

Characterization of the genomic and transcriptomic landscape of invasive non-mucinous lung adenocarcinoma based on IASLC grading.

BACKGROUND: The IASLC grading system has prognostic utility and potential therapeutic implications in invasive non-mucinous lung adenocarcinoma (LUAD), but the molecular basis underlying the grading spectrum remains unclear. METHODS: We performed whole-genome sequencing in 138 Chinese patients with invasive non-mucinous LUAD and RNA sequencing of 96 matched tumor-normal tissue pairs to systematically characterize the molecular features across grades, including coding driver events, mutational signatures, non-coding regulatory disruptions, and transcriptional programs. RESULTS: Compared with Grade 1-2 tumors, Grade 3 LUADs exhibited heightened invasive potential, manifested by more advanced stage, more frequent spread through air spaces, and independently worse survival. Grade 3 tumors had elevated tumor mutational burden and were enriched for alterations in genome maintenance and cell-cycle genes, including TP53, as well as genes implicated in DNA damage response, including ZFHX4. APOBEC-associated mutagenesis was selectively enriched in Grade 3 tumors independent of smoking status, consistent with an instability-associated phenotype. Recurrent non-coding regulatory disruptions affected lung lineage-defining genes, particularly surfactant-associated genes, and were correlated with reduced expression. Transcriptomic profiling revealed epithelial dedifferentiation, loss of pulmonary homeostatic programs, and activation of proliferative and stress-related pathways. Notably, MUC16 emerged as a convergent event linking genomic and transcriptional dysregulation, with coding mutations associated with higher expression and increased expression in Grade 3 tumors correlating with the proportion of high-grade histologic patterns. CONCLUSIONS: These findings provide a molecular framework for the IASLC grading spectrum and identify Grade 3 LUAD as a distinct instability-associated and dedifferentiated biological state.

IASLC grading↗
PubMed1979

Conformation of exocyclic amino groups in purines and pyrimidines: crystal structure and conformation of 1-methyl-N4-hydroxycytosine hydrochloride.

The hydrochloride salt of 1-methyl-N4-hydroxycytosine crystallizes in the triclinic space group P1 with cell dimensions: a = 8.232(1), b = 9.293(1), c = 5.416(1) A (1 A = 0.1 nm); alpha = 91.95(1), beta = 91.72(2), gamma = 71.56(1) degrees (SE in parentheses). The structure was solved by direct methods and refined to R = 3.7% for 1514 reflections. Despite the absence of an intramolecular hydrogen bond in the solid state, the N4-hydroxy substituent is syn to the ring N(3). This conformation, which probably prevails also in the neutral form, is of relevance to the mechanism of attack of cytosine by hydroxylamine, known to involve predominantly the cytosine cation, as well as to the mechanism of hydroxylamine mutagenesis. Such conformational aspects are also relevant to other phenomena, including translation and restriction.

Crystallization↗
PubMed1978

Escherichia coli mutants defective in dipeptidyl carboxypeptidase.

Two independent mutants of Escherichia coli deficient in dipeptidyl carboxypeptidase activity (Dep-) were isolated after mutagenesis with ethyl methanesulfonate. Mating experiments and introduction of specific episomes indicated that the responsible gene was located at approximately 27--31 min on the E. coli chromosome. The Dep- mutants differed from the parental strain in their inability to grow with N-acetylalanylalanylalanine as the sole nitrogen source. Revertants selected for growth on this substrate of the enzyme were found to have reacquired the activity. Enzyme activity was highly sensitive to inhibition by 1-(D-3-mercapto-2-methylpropanoyl)-L-proline (SQ 14225), a potent inhibitor of mammalian dipeptidyl carboxypeptidase (angiotensin-converting enzyme, peptidyl dipeptidase, EC 3.4.15.1). This compound also reduced the rate of growth of the wild type with N-acetylalanylalanylalanine but not with ammonium sulfate. A fraction of the enzyme was released into the medium by osmotic shock, indicating that its presence in the periplasmic space may account for growth with N-acetylated peptides that cannot be taken up by E. coli. In addition to providing information about the specific role of this exopeptidase in E. coli, the Dep- mutants may prove useful for delineating the regulation and cellular function of dipeptidyl carboxypeptidases in higher organisms.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2025

Turbo-charging crop improvement: harnessing multiplex editing for polygenic trait engineering and beyond.

Multiplex CRISPR editing has emerged as a transformative platform for plant genome engineering, enabling the simultaneous targeting of multiple genes, regulatory elements, or chromosomal regions. This approach is effective for dissecting gene family functions, addressing genetic redundancy, engineering polygenic traits, and accelerating trait stacking and de novo domestication. Its applications now extend beyond standard gene knockouts to include epigenetic and transcriptional regulation, chromosomal engineering, and transgene-free editing. These capabilities are advancing crop improvement not only in annual species but also in more complex systems such as polyploids, undomesticated wild relatives, and species with long generation times. At the same time, multiplex editing presents technical challenges, including complex construct design and the need for robust, scalable mutation detection. We discuss current toolkits and recent innovations in vector architecture, such as promoter and scaffold engineering, that streamline workflows and enhance editing efficiency. High-throughput sequencing technologies, including long-read platforms, are improving the resolution of complex editing outcomes such as structural rearrangements-often missed by standard genotyping-when targeting repetitive or tandemly spaced loci. To fully realize the potential of multiplex genome engineering, there is growing demand for user-friendly, synthetic biology-compatible, and scalable computational workflows for gRNA design, construct assembly, and mutation analysis. Experimentally validated inducible or tissue-specific promoters are also highly desirable for achieving spatiotemporal control. As these tools continue to evolve, multiplex CRISPR editing is poised to become a foundational technology of next-generation crop improvement to address challenges in agriculture, sustainability, and climate resilience.

Gene Editing↗
PubMedDate not supplied

Ethylene oxide: toxicology review and field study results of hospital use.

Ethylene oxide (ETO) is used extensively within health care facilities for sterilization of equipment and supplies. Alternative chemicals or processes have, in themselves, serious limitations or health hazards. NIOSH recognizes, therefore, that the continued use of ETO as a gaseous sterilant is highly desirable in many situations. Recent results of tests for mutagenesis have increased the concern for potential health havards associated with exposure to ETO. In order to assess the potential for exposure and associated hazards, NIOSH prepared a "Special Occupational Hazard Review with Control Recommendations for the Use of ETO as a Sterilant in Medical Facilities," DHEW (NIOSH) Publication No. 77-200 (Aug. 1977). An assessment was made of the evidence for toxic effects of ETO, especially with respect to mutagenic, teratogenic, and carcinogenic potentials. Additionally, a limited field survey was conducted by NIOSH to document the use, problems, and potential for human exposure in medical facilities. Based on this review, measures for control of control of occupational exposure have been recommended. The report includes a summary of the airborne ETO concentrations measured within health care facilities as part of the field survery. NIOSH estimates that there are in excess of ten thousand ETO sterilizers in use in U.S. health care facilities, and that approximately 75 thousand workers are potentially exposed to ETO in those facilities. Reasons for the unnecessary exposure of personnel were found to include: improper or inadequate ventilation of sterilizers, aerators, and working spaces; improper handling and/or storage of sterilized items; untrained workers operating some sterilization equipment; improper operating techniques leading to mishandling of some ETO sterilizing equipment; poor design of the sterilization facility; and design limitations of the sterilization equipment.

Adult↗