MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment

被引:176
作者
Bian, Lei [1 ]
Meng, Yiling [1 ]
Zhang, Meichao [1 ]
Li, Dong [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Radiat Oncol, Sch Med, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
MRN complex; DNA damage response; tumorigenesis; chemotherapy; radiotherapy; NIJMEGEN BREAKAGE SYNDROME; SEROUS OVARIAN-CANCER; BREAST-CANCER; MRE11; NUCLEASE; MRN COMPLEX; HOMOLOGOUS RECOMBINATION; ONCOLYTIC ADENOVIRUS; GENE-EXPRESSION; CLINICAL PRESENTATION; MOLECULAR DISRUPTION;
D O I
10.1186/s12943-019-1100-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Genome instability is a hallmark of cancer cells and can be accelerated by defects in cellular responses to DNA damage. This feature of malignant cells opens new avenues for tumor targeted therapy. MRE11-RAD50-NBS1 complex plays a crucial role in sensing and repair of DNA damage. Through interacting with other important players of DNA damage response, MRE11-RAD50-NBS1 complex is engaged in various DNA damage repair pathways. Mutations in any member of this complex may lead to hypersensitivity to genotoxic agents and predisposition to malignancy. It is assumed that the defects in the complex may contribute to tumorigenesis and that treatments targeting the defect may be beneficial to cancer patients. Here, we summarized the recent research findings of the role of MRE11-RAD50-NBS1 complex in tumorigenesis, cancer treatment and discussed the potential approaches of targeting this complex to treat cancer.
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页数:14
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