Search arXiv⌕ Search
Home/Archive/arXiv

arXiv · 2503.21837

Impact of Oxygen on DNA Damage Distribution in 3D Genome and its Correlation to Oxygen Enhancement Ratio after High-LET Irradiation

Ankang Hu·Wanyi Zhou·Xiyu Luo·Rui Qiu·Junli Li
View original source ↗Read source document ↗Export metadata ↓

Abstract

The variation of the oxygen enhancement ratio (OER) across linear energy transfer (LET) currently lacks a comprehensive mechanistic interpretation and a mechanistic model. Our earlier research revealed a significant correlation between the distribution of double-strand breaks (DSBs) within 3D genome and radiation-induced cell death, which offers valuable insights into the oxygen effect. We propose a model where the reaction of oxygen is represented as the probability of inducing DNA strand breaks. Then it is integrated into a track-structure Monte Carlo simulation to investigate the impact of oxygen on the distribution of DSBs within 3D genome. Using the parameters from our previous study, we calculate the OER values related to cell survival. Results show that the incidence ratios of clustered DSBs within a single topologically associating domain (TAD) (case 2) and within frequently interacting TADs (case 3) under aerobic and hypoxic conditions align with the trend in the OER of cell survival across LET. Our OER curves exhibit good correspondence with experimental data. This study provides a potentially mechanistic explanation for changes in OER across LET. High-LET irradiation leads to dense ionization events, resulting in an overabundance of lesions that readily induce case 2 and case 3, which have substantially higher probabilities of cell killing than other damage patterns. This may contribute to the main mechanism governing the variation of OER for high LET. Our study further underscores the importance of the DSB distribution within 3D genome in the context of radiation-induced cell death.

Explore related subjects

physics.bio-phphysics.med-ph

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ankang Hu, Wanyi Zhou, Xiyu Luo, Rui Qiu, Junli Li. 2026-06-10. Impact of Oxygen on DNA Damage Distribution in 3D Genome and its Correlation to Oxygen Enhancement Ratio after High-LET Irradiation. https://doi.org/10.1667/rade-25-00093.1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Signature of mechanically induced cell extrusions in cell size distribution

How a growing tissue organizes its own homeostatic state is a central question in the physics of living matter. We show that when a growing epithelial sheet counteracts increasing cell density by mechanically squeezing cells out of its plane, a homeostatic in-plane pressure emerges as a generalization of a yield stress. We find that in the quasistatic growth limit the homeostatic state is marginally stable, with a pseudogap in the distribution of local distances to the extrusion threshold pressure. Because such mechanically induced extrusions arise from an instability of individual cells, the pseudogap is imprinted in the distribution of cell areas. This provides an image-based way to test for presence of mechanically induced extrusions and we identify this signature in the developing wing epithelium of \textit{D.~melanogaster}. We expect the same principles to apply to confined three-dimensional tissues.

physics.bio-ph↗
arXiv2026

Towards Accurate Prediction of Mutation-Induced Changes in Protein Structure

Proteins can possess numerous mutations relative to their wild-type amino acid sequences with minimal impact to their structure and function. However, in other cases, even a single amino acid mutation relative to the wild-type sequence can lead to a large change in structure or even a disease phenotype. While the accuracy of wild-type protein structure prediction has improved significantly in recent years, it remains difficult to accurately predict the structure of mutant proteins. Here, we characterize the local mutation-induced structural changes in proteins for a dataset of wildtype and the corresponding single-amino acid mutant x-ray crystal structures from the Protein Data Bank (PDB). We find that mutation-induced structural changes in these proteins are localized at the site of the mutation, decaying rapidly with increasing spatial distance from the mutation site. In addition, we evaluate how well AlphaFold3 can recapitulate the observed mutation-induced structural deformations in the x-ray crystal structures. We find that the accuracy of the AlphaFold3 predictions decreases strongly with increasing mutation-induced deformation. In contrast to the results for AlphaFold3, the Pearson correlation between a single physical feature, i.e. the change in solvent accessibility, and the mutation-induced deformation does not depend on the magnitude of the deformation. Our results and analyses provide a framework for further studies aimed at predicting the structural changes in proteins caused by single amino acid mutations.

physics.bio-ph↗
arXiv2026

Biology and Physics

This article frames the relation between biology and physics by characterizing the former as a subdiscipline rather than a special case of the latter. To do this, we posit biological physics as the science of living matter in contrast to classic biophysics, the study of organismal properties by physical techniques. At the scale of the individual cell, living matter is nonunitary, i.e., not composed of aggregated subunits, and has features (e.g., intracellular organizational arrangements and biomolecular condensates) that are unlike any materials of the nonliving world. In transiently or constitutively multicellular forms (social microorganisms, animals, plants), living matter sustains physical processes that are generic (shared with nonliving matter, e.g., subunit communication by molecular diffusion in cellular slime molds), biogeneric (analogous to nonliving matter but realized through cellular activities, e.g., subunit demixing in animal embryos) or nongeneric (pertaining to sui generis materials, e.g., budding of active solids in plants). This "forms of matter" perspective is philosophically situated in the dialectical materialism of Engels and Hessen and the multilevel physicalism of Neurath and the logical empiricists. We counterpose this view to informationism and to genetic and other hierarchically reductionist physical theories of biological systems and highlight open questions regarding incompletely characterized and enigmatic forms of living matter.

physics.bio-ph↗