Replication-stress-associated DSBs induced by ionizing radiation risk genomic destabilization and associated clonal evolution.
Replication-stress-associated DSBs induced by ionizing radiation risk genomic destabilization and associated clonal evolution.
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DOI：
10.1016/j.isci.2021.102313
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发表时间：
2021-04-23
期刊：
影响因子：
5.8
通讯作者：
Yoshioka KI
中科院分区：
文献类型：
--
作者：
Matsuno Y;Hyodo M;Suzuki M;Tanaka Y;Horikoshi Y;Murakami Y;Torigoe H;Mano H;Tashiro S;Yoshioka KI
暴露于电离辐射与患癌症的风险有关。尽管多种类型的DNA损伤是由辐射引起的，但这种损伤与癌症风险之间的关系尚不清楚。本研究表明，在辐射直接引起的双链断裂（dsb）修复后，由于复制应激相关的dsb （rs- dsb）的积累，受辐射的细胞进入基因组不稳定风险较高的状态，最终导致细胞的克隆进化，其防御系统被废除。在大剂量（0.25 - 2gy）和剂量率（1.39-909毫戈瑞/分钟）范围内观察到这些效应，但在高剂量照射下没有观察到这些效应，因为高剂量照射会导致永久性细胞周期停滞。由此产生的基因组不稳定也增加了诱导单核苷酸变异（snv）的风险，包括辐射相关的snv，以及染色体的结构改变。因此，辐射相关的风险可归因于rs-DSB积累和由此产生的基因组不稳定。与复制应激相关的dsb在暴露于电离辐射后积累，这种dsb有基因组不稳定和相关突变的风险，由此产生的基因组重排和突变导致无性系进化。辐射相关的风险在大范围的辐射剂量和剂量率下出现；癌症;细胞生物学
Exposure to ionizing radiation is associated with cancer risk. Although multiple types of DNA damage are caused by radiation, it remains unknown how this damage is associated with cancer risk. Here, we show that after repair of double-strand breaks (DSBs) directly caused by radiation (dir-DSBs), irradiated cells enter a state at higher risk of genomic destabilization due to accumulation of replication-stress-associated DSBs (rs-DSBs), ultimately resulting in clonal evolution of cells with abrogated defense systems. These effects were observed over broad ranges of radiation doses (0.25–2 Gy) and dose rates (1.39–909 mGy/min), but not upon high-dose irradiation, which caused permanent cell-cycle arrest. The resultant genomic destabilization also increased the risk of induction of single-nucleotide variants (SNVs), including radiation-associated SNVs, as well as structural alterations in chromosomes. Thus, the radiation-associated risk can be attributed to rs-DSB accumulation and resultant genomic destabilization. Replication-stress-associated DSBs accumulate after exposure to ionizing radiation Such DSBs risk genomic destabilization and associated mutagenesis The resulting genomic rearrangements and mutations lead to clonal evolution The radiation-associated risks arise at wide ranges of radiation doses and dose rates Biological Sciences ; Cancer ; Cell Biology
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染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
21.3
作者：
Glück S;Guey B;Gulen MF;Wolter K;Kang TW;Schmacke NA;Bridgeman A;Rehwinkel J;Zender L;Ablasser A
通讯作者：
Ablasser A
影响因子：
64.8
作者：
Dou Z;Ghosh K;Vizioli MG;Zhu J;Sen P;Wangensteen KJ;Simithy J;Lan Y;Lin Y;Zhou Z;Capell BC;Xu C;Xu M;Kieckhaefer JE;Jiang T;Shoshkes-Carmel M;Tanim KMAA;Barber GN;Seykora JT;Millar SE;Kaestner KH;Garcia BA;Adams PD;Berger SL
通讯作者：
Berger SL
由复制应力诱导的DNA病变触发有丝分裂畸变和四倍体发育。
影响因子：
3.7
作者：
Ichijima Y;Yoshioka K;Yoshioka Y;Shinohe K;Fujimori H;Unno J;Takagi M;Goto H;Inagaki M;Mizutani S;Teraoka H
通讯作者：
Teraoka H
影响因子：
5.6
作者：
Yoshioka KI;Atsumi Y;Fukuda H;Masutani M;Teraoka H
通讯作者：
Teraoka H