1. 国家自然科学基金面上项目: 酵母反转座抑制因子Rtt105在同源重组和维持基因组稳定性中的作用与机制研究. 2021-2024 (主持)
2. 国家自然科学基金面上项目: 酵母泛素连接酶Bre1及其介导的H2B泛素化修饰在DNA双链断裂修复中的作用与机制研究. 2019-2022 (主持)
3. 国家重点研发计划子课题:中内胚层来源组织器官间互作对干细胞命运的转录调控. 2021-2026 (主持)
4. 国家自然科学基金面上项目: 酵母溴结构域蛋白Bdf1在DNA双链断裂修复中的作用与机制研究. 2017-2020 (主持)
5. 国家自然科学基金面上项目: 细胞周期激酶Cdk1和周期蛋白在DNA双链断裂修复中的作用. 2015-2018 (主持)
6. 国家重大基础研究计划子项目课题:细胞周期激酶和 DNA 损伤检查点蛋白在 DSB修复中的作用. 2015-2019 (主持)
维持细胞基因组的完整性与稳定性对于细胞正常生长、分化及增殖至关重要。真核细胞依赖于高度精密的DNA损伤修复系统和染色体分离机制来确保基因组的完整性和稳定性。当DNA损伤修复或有丝分裂存在缺陷时,会导致基因突变、染色体结构或数量异常及基因组稳定性失控等系列问题,最终引发细胞发生癌变、死亡。基因组稳定性失调可能会导致肿瘤发生、免疫缺陷、生殖障碍、衰老及人类遗传病的发生。
DNA损伤修复和有丝分裂机制在进化过程中高度保守。本实验室以人类细胞和酵母为材料,结合小鼠模型,综合利用遗传学、生化与分子生物学、细胞生物学及现代单分子技术与方法,围绕DNA修复、有丝分裂与基因组稳定性中的重要科学问题开展研究。
Guangxue Liu#, Jimin Li#, Boxue He, Jiaqi Yan, Jingyu Zhao, Xuejie Wang, Xiaocong Zhao, Yeyao Wu, Xiaoli Gan, Simin Zhang, Chun Zhou, Xiangpan Li, Xinghua Zhang, Xuefeng Chen*. Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases. Nature Communications, 2023 (accepted)
Jimin Li, Jingyu Zhao, Xiaoli Gan, Yanyan Wang, Donghao Jiang, Liang Chen, Fangwei Wang, Jingyan Xu, Huadong Pei, Jun Huang, Xuefeng Chen*. The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair. Proc Natl Acad Sci USA, 2023 (In press)
Xiaoli Gan, Yueyue Zhang, Donghao Jiang, Jingyao Shi, Han Zhao, Chengyu Xie, Yanyan Wang, Jingyan Xu, Xinghua Zhang, Gang Cai, Hailong Wang, Jun Huang, Xuefeng Chen*. Proper RPA acetylation promotes accurate DNA replication and repair. Nucleic Acids Research, 2023 (In press)
Meng Shi# , Jiaqi Zhao#, Simin Zhang#, Wei Huang , Mengfei Li, Xue Bai , Wenxue Zhang, Kai Zhang , Xuefeng Chen*, Song Xiang*. Structural basis for the Rad6 activation by the Bre1 N-terminal domain. Elife, 2023, 12: e84157.
Xuejie Wang
#
, Yang Dong
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, Xiaocong Zhao
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, Jinbao Li, Jordan Lee, Zhenxin Yan, Shuangshuang Yang, Wenqiang Wu, Ximiao Hou, Guangxue Liu, Yueyue Zhang, Lun Song, Gang Cai, Qing Li, Grzegorz Ira, Xinghua Zhang*, Xuefeng Chen
*
. Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA binding factor RPA.
Proc Natl Acad Sci USA
, 2021, 118: e2106393118.
Haoyang Peng, Simin Zhang, Yihan Peng, Shuangyi Zhu, Xin Zhao, Xiaocong Zhao, Shuangshuang Yang, Guangxue Liu, Yang Dong, Xiaoli Gan, Qing Li, Xinhua Zhang, Huadong Pei*, Xuefeng Chen*. Yeast Bromodomain Factor 1 and Its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination. Advanced Science, 2021, e2100753
Guangxue Liu, Jiaqi Yan, Xuejie Wang, Junliang Chen, Xin Wang, Yang Dong, Simin Zhang, Xiaoli Gan, Jun Huang, Xuefeng Chen*. RPA-Mediated Recruitment of Bre1 Couples Histone H2B Ubiquitination to DNA Replication and Repair. Proc Natl Acad Sci USA, 2021,118(8): e2017497118.
Sihao Zheng, Dan Li, Zhen Lu, Guangxue Liu, Meng Wang, Min Wang, Yang Dong, Jingyao Li, Haoyang Peng, Xuejie Wang, Grzegorz Ira, Guohong Li, Xuefeng Chen*. Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks. Nucleic Acids Research, 2018, 46(21):11326-11339.
Xuefeng Chen*, Hengyao Niu, Yang Yu, Jingjing Wang, Shuangyi Zhu, Jianjie Zhou, Alma Papusha, Dandan Cui, Xuewen Pan, Youngho Kwon, Patrick Sun* and Grzegorz Ira*. Enrichment of Cdk1-cyclins at DNA double-strand breaks stimulates Fun30 phosphorylation and DNA end resection. Nucleic Acids Research, 2016, 44: 2742-2753
Xuefeng Chen, Dandan Cui, Alma Papusha, Xiaotian Zhang, Chia-Dwo Chu, Jiangwu Tang, Kaifu Chen, Xuewen Pan, Grzegorz Ira. The Fun30 ATP-dependent nucleosome remodeler promotes resection of DNA double-strand break ends. Nature, 2012,489(7417): 576-580
Xuefeng Chen, Hengyao Niu, Woo-Hyun Chung, Zhu Zhu, Alma Papusha, Eun Yong Shim, Sang Eun Lee, Patrick Sungand Grzegorz Ira. Cell cycle regulation of DNA double-strand break end resection by Cdk1-dependent Dna2 phosphorylation. Nature Structural & Molecular Biology, 2011, 18(9):1015-1019
Marenda A. Wilson,YoungHo Kwon,Yuanyuan Xu, Woo-Hyun Chung, Peter Chi,Hengyao Niu, Ryan Mayle, Xuefeng Chen, Anna Malkova, Patrick Sung, Grzegorz Ira. Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration. Nature, 2013, 502 (7471): 393-396