| Autor: |
Jinwook Choi, Joon-Goon Kim, Young Seo Kim, Eunji Kim, Hyun Woo Kwon, Kijong Yi, On Vox Yi, Joonoh Lim, Ji Hyun Chang, Tae-You Kim, Joo-Hyeon Lee, Hyo-Jin Kim, Jeonghwan Youk, Tae Gen Son, Yeong-Rok Kang, Hyunsook Lee, Su Yeon Kim, Ryul Kim, Young Seok Ju, Si Ho Choi, Dong Soo Lee, Kyung Su Kim, Bon-Kyoung Koo, Min Ji Bae, Eon Chul Han, Dong-Wook Min, Chang Geun Lee, Eun-Seok Lee, Sara Jeon, Taeyun Ku, Hyelin Na, Seongyeol Park, Young-Won Cho |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.01.12.426324 |
| Popis: |
Whole-genome sequencing (WGS) of human tumors and normal cells exposed to various carcinogens has revealed distinct mutational patterns that provide deep insights into the DNA damage and repair processes. Although ionizing radiation (IR) is conventionally known as a strong carcinogen, its genome-wide mutational impacts have not been comprehensively investigated at the single-nucleotide level. Here, we explored the mutational landscape of normal single-cells after exposure to the various levels of IR. On average, 1 Gy of IR exposure generated ∼16 mutational events with a spectrum consisting of predominantly small nucleotide deletions and a few characteristic structural variations. In ∼30% of the post-irradiated cells, complex genomic rearrangements, such aschromoplexy, chromothripsis, and breakage-fusion-bridge cycles, were resulted, indicating the stochastic and chaotic nature of DNA repair in the presence of the massive number of concurrent DNA double-strand breaks. These mutational signatures were confirmed in the genomes of 22 IR-induced secondary malignancies. With high-resolution genomic snapshots of irradiated cells, our findings provide deep insights into how IR-induced DNA damage and subsequent repair processes operate in mammalian cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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