Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
Abstract
:1. Introduction
2. Results
2.1. Modeling of Chromosome Aberrations Based on Polymer Physics of Chromosomes
2.2. Physical Modeling of Hi-C Data Reveals Heteropolymer Globule Organization of Mouse Chromosomes
2.3. Structural Organization of Mouse Chromosomes Promotes IR-Recurrent Aberrations
2.4. Impact of Targeted vs. Nontargeted DSBs on Translocation Breakpoint Distribution
2.5. Single-Cell Variability of Cis-Translocation Breakpoints
2.6. Heterogeneity in Spatial Chromosome Organization among Individual Cells and Breakpoint Distributions
2.7. Translocation Breakpoint Distribution Depends on Movement of Damaged Loci
3. Discussion
4. Materials and Methods
4.1. Polymer Modeling of Chromosome Structure
- The initial coefficients are equal for all element pairs, U0 = 1.2 kT.
- The ensemble of up to 4000 conformations is simulated.
- The contact map with 100 kb resolution is obtained. Pearson’s correlation between the simulated map and the experimental one is calculated.
- If Pearson’s correlation between the contact maps ceases to improve, the simulation is stopped. Otherwise, for each element pair (i,j), the coefficient in the attraction potential increases if the simulated contact frequency is lower than the experimental one and decreases if it is higher.
- Return to step 2.
4.2. Simulation of Trial Structures
4.3. Modeling of Intrachromosomal Aberrations by the Contact-First Mechanism
4.4. Aberration Modeling in the Absence of Irradiation
4.5. CA Modeling by the Breakage-First Mechanism
4.6. CA Modeling Incorporating Conformational Transitions
4.7. Data Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Relative Fluctuations, SD/Mean |
---|---|
Number of total contacts in chromosome | 0.014 |
Number of contacts with I-SceI site | 0.33 |
Number of lesion contacts with I-SceI site (5 Gy) | 4.32 |
Number of breakpoints (5 Gy) | 110.6 |
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Eidelman, Y.; Salnikov, I.; Slanina, S.; Andreev, S. Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage. Int. J. Mol. Sci. 2021, 22, 12186. https://doi.org/10.3390/ijms222212186
Eidelman Y, Salnikov I, Slanina S, Andreev S. Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage. International Journal of Molecular Sciences. 2021; 22(22):12186. https://doi.org/10.3390/ijms222212186
Chicago/Turabian StyleEidelman, Yuri, Ilya Salnikov, Svetlana Slanina, and Sergey Andreev. 2021. "Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage" International Journal of Molecular Sciences 22, no. 22: 12186. https://doi.org/10.3390/ijms222212186