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学科主题基础医学
PTIP associates with Artemis to dictate DNA repair pathway choice
Wang, Jiadong1,2; Aroumougame, Asaithamby3; Lobrich, Markus4; Li, Yujing2; Chen, David3; Chen, Junjie2; Gong, Zihua2
关键词Ptip Artemis 53bp1 Brca1 Dna Repair Parp Inhibition
刊名GENES & DEVELOPMENT
2014-12-15
DOI10.1101/gad.252478.114
28期:24页:2693-2698
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Developmental Biology ; Genetics & Heredity
资助者National Institutes of Health ; Basser Team Science Award ; Era of Hope Scholar award from the Department of Defense ; M.D. Anderson Cancer Center ; National Institutes of Health ; Basser Team Science Award ; Era of Hope Scholar award from the Department of Defense ; M.D. Anderson Cancer Center
研究领域[WOS]Cell Biology ; Developmental Biology ; Genetics & Heredity
关键词[WOS]LYSINE-4 METHYLTRANSFERASE COMPLEX ; REPLICATION CHECKPOINT CONTROL ; BRCA-MUTATED BREAST ; END RESECTION ; PROTEIN ; RECOMBINATION ; BINDING ; TOPBP1 ; RIF1 ; AUTOPHOSPHORYLATION
英文摘要

PARP inhibitors (PARPis) are being used in patients with BRCA1/2 mutations. However, doubly deficient BRCA1(-/-) 53BP1(-/-) cells or tumors become resistant to PARPis. Since 53BP1 or its known downstream effectors, PTIP and RIF1 (RAP1-interacting factor 1 homolog), lack enzymatic activities directly implicated in DNA repair, we decided to further explore the 53BP1-dependent pathway. In this study, we uncovered a nuclease, Artemis, as a PTIP-binding protein. Loss of Artemis restores PARPi resistance in BRCA1-deficient cells. Collectively, our data demonstrate that Artemis is the major downstream effector of the 53BP1 pathway, which prevents end resection and promotes nonhomologous end-joining and therefore directly competes with the homologous recombination repair pathway.

语种英语
所属项目编号CA089239 ; CA092312 ; CA100109 ; W81XWH-05-1-0470 ; CA016672
资助者National Institutes of Health ; Basser Team Science Award ; Era of Hope Scholar award from the Department of Defense ; M.D. Anderson Cancer Center ; National Institutes of Health ; Basser Team Science Award ; Era of Hope Scholar award from the Department of Defense ; M.D. Anderson Cancer Center
WOS记录号WOS:000346335700002
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被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52610
专题基础医学院_北京大学系统生物医学研究所
作者单位1.Peking Univ, Inst Syst Biomed, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China
2.Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA
3.Univ Texas SW Med Ctr Dallas, Dept Radiat Biol, Dallas, TX 75390 USA
4.Tech Univ Darmstadt, Radiat Biol & DNA Repair Lab, D-64287 Darmstadt, Germany
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Wang, Jiadong,Aroumougame, Asaithamby,Lobrich, Markus,et al. PTIP associates with Artemis to dictate DNA repair pathway choice[J]. GENES & DEVELOPMENT,2014,28(24):2693-2698.
APA Wang, Jiadong.,Aroumougame, Asaithamby.,Lobrich, Markus.,Li, Yujing.,Chen, David.,...&Gong, Zihua.(2014).PTIP associates with Artemis to dictate DNA repair pathway choice.GENES & DEVELOPMENT,28(24),2693-2698.
MLA Wang, Jiadong,et al."PTIP associates with Artemis to dictate DNA repair pathway choice".GENES & DEVELOPMENT 28.24(2014):2693-2698.
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