文献类型： 外文期刊

作者： Kang, Xing ¹ ; Li, Xinran ¹ ; Zhou, Jiaqi ¹ ; Zhang, Yang ¹ ; Qiu, Lingyu ¹ ; Tian, Congcong ¹ ; Deng, Zhiwen ³ ; Liang, Xiaoyan ¹ ; Zhang, Ziwei ¹ ; Du, Songlin ⁴ ; Hu, Suili ¹ ; Wang, Nan ¹ ; Yue, Zhen ¹ ; Xu, Yajing ¹ ; Gao, Yuan ⁶ ; Dai, Junbiao ⁷ ; Wang, Zhiquan ¹⁰ ; Yu, Chuanhe ¹¹ ; Chen, Jinyi ¹ ; Wu, Yuchun ¹ ; Chen, Liangming ¹ ; Yao, Yuan ¹ ; Yao, Sitong ¹ ; Yang, Xinran ¹ ; Yan, Lixia ¹ ; Wen, Qing ¹ ; Depies, Olivia M. ¹⁰ ; Chan, Kuiming ¹³ ; Liang, Xiaohuan ⁵ ; Li, Gang ¹⁴ ; Zi, Zhike ¹ ; Liu, Xiangyu ³ ; Gan, Haiyun ¹ ;

作者机构： 1.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Key Lab Quantitat Engn Biol,Guangdong Prov Key Lab, Shenzhen, Peoples R China

2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

3.Shenzhen Univ, Int Canc Ctr, Guangdong Prov Key Lab Reg Immun & Dis, Marshall Lab Biomed Engn,Hlth Sci Ctr, Shenzhen, Peoples R China

4.Northwest A&F Univ, Coll Anim Sci & Technol, Xianyang 712100, Shaanxi, Peoples R China

5.South China Agr Univ, Coll Vet Med, Guangzhou, Peoples R China

6.Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH USA

7.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, CAS Key Lab Quantitat Engn Biol,Guangdong Prov Key, Shenzhen, Peoples R China

8.Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Shenzhen Key Lab Synthet Genom, Shenzhen, Peoples R China

9.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch, Guangdong Lab Lingnan Modern Agr,Key Lab Synthet B, Shenzhen, Peoples R China

10.Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA

11.Univ Minnesota, Hormel Inst, Austin, MN USA

12.Qingdao Univ, Sch Basic Med, Qingdao, Peoples R China

13.City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China

14.Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Inst Translat Med, Macau, Peoples R China

期刊名称：CELL （ 影响因子：42.5； 五年影响因子：48.9 ）

ISSN： 0092-8674

年卷期： 2025 年 188 卷 13 期

页码：

收录情况： SCI

摘要： Extrachromosomal DNA (ecDNA) drives the evolution of cancer cells. However, the functional significance of ecDNA and the molecular components involved in its replication and maintenance remain largely unknown. Here, using CRISPR-C technology, we generated ecDNA-carrying (ecDNA+) cell models. By leveraging these models alongside other well-established systems, we demonstrated that ecDNA can replicate and be maintained in ecDNA+ cells. The replication of ecDNA activates the ataxia telangiectasia mutated (ATM)-mediated DNA damage response (DDR) pathway. Topoisome rases, such as TOP1 and TOP2B, play a role in ecDNA replication-induced DNA double-strand breaks (DSBs). A subset of these elevated DSBs persists into the mitotic phase and is primarily repaired by the alternative non-homologous end joining (alt-NHEJ) pathway, which involves POLO and LIG3. Correspondingly, ecDNA maintenance requires DDR, and inhibiting DDR impairs the circularization of ecDNA. In summary, we demonstrate reciprocal interactions between ecDNA maintenance and DDR, providing new insights into the detection and treatment of ecDNA+ tumors.