ASPM promotes homologous recombination-mediated DNA repair by safeguarding BRCA1 stability.
ASPM promotes homologous recombination-mediated DNA repair by safeguarding BRCA1 stability.
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ASPM 通过保护 BRCA1 稳定性来促进同源重组介导的 DNA 修复。
DOI：
10.1016/j.isci.2021.102534
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发表时间：
2021-06-25
期刊：
影响因子：
5.8
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Xu S;Wu X;Wang P;Cao SL;Peng B;Xu X
通过同源重组（HR）修复DNA双链断裂（DSB）对于确保基因组稳定性是必不可少的。异常纺锤状小头畸形相关基因（ASPM）编码一种纺锤体蛋白，通常与原发性小头畸形有关。我们发现ASPM以PARP 2依赖的方式被募集到DNA损伤的位点。ASPM与BRCA 1及其E3连接酶HERC 2相互作用，阻止HERC 2接近BRCA 1，确保BRCA 1的稳定性。ASPM表达的抑制促进HERC 2介导的BRCA 1降解，损害HR修复效率和染色体稳定性，并使癌细胞对电离辐射敏感。此外，我们观察到ASPM和PARP抑制在杀死癌细胞方面的协同效应。这项研究揭示了ASPM通过确保BRCA 1稳定性促进HR介导的DSB修复的新功能。ASPM可能构成一个有前途的目标，为合成致死为基础的癌症治疗。ASPM以PARP 2依赖性方式被募集到DNA损伤位点。ASPM促进DSB末端切除以促进HR修复。ASPM阻止HERC 2进入BRCA 1，确保BRCA 1的稳定性。ASPM的抑制使癌细胞对电离辐射和PARP抑制剂敏感。分子生物学;细胞生物学;细胞生物学功能
DNA double-strand break (DSB) repair by homologous recombination (HR) is essential for ensuring genome stability. Abnormal spindle-like microcephaly-associated (ASPM) gene encodes a spindle protein that is commonly implicated in primary microcephaly. We found that ASPM is recruited to sites of DNA damage in a PARP2-dependent manner. ASPM interacts with BRCA1 and its E3 ligase HERC2, preventing HERC2 from accessing to BRCA1 and ensuring BRCA1 stability. Inhibition of ASPM expression promotes HERC2-mediated BRCA1 degradation, compromises HR repair efficiency and chromosome stability, and sensitizes cancer cells to ionizing radiation. Moreover, we observed a synergistic effect between ASPM and PARP inhibition in killing cancer cells. This research has uncovered a novel function for ASPM in facilitating HR-mediated repair of DSBs by ensuring BRCA1 stability. ASPM might constitute a promising target for synthetic lethality-based cancer therapy. ASPM is recruited to sites of DNA damage in a PARP2-dependent manner. ASPM promotes DSB-end resection to facilitate HR repair. ASPM prevents HERC2 from accessing to BRCA1 and ensuring BRCA1 stability. Inhibition of ASPM sensitizes cancer cells to ionizing radiation and PARP inhibitor. Molecular biology; Cell biology; Functional aspects of cell biology
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影响因子：
3.7
作者：
Alsiary R;Brüning-Richardson A;Bond J;Morrison EE;Wilkinson N;Bell SM
通讯作者：
Bell SM
人CTIP介导DNA终端切除和双链断裂修复的细胞周期控制。
DOI：
10.1074/jbc.m808906200
发表时间：
2009-04-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huertas P;Jackson SP
通讯作者：
Jackson SP
DOI：
10.1083/jcb.201007107
发表时间：
2010-11-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cizmecioglu O;Arnold M;Bahtz R;Settele F;Ehret L;Haselmann-Weiss U;Antony C;Hoffmann I
通讯作者：
Hoffmann I
影响因子：
4.2
作者：
Korhonen, L;Brännvall, K;Lindholm, D
通讯作者：
Lindholm, D
影响因子：
11.5
作者：
Lin, Shih-Yeh;Pan, Hung-Wei;Hsu, Hey-Chi
通讯作者：
Hsu, Hey-Chi