Abstract：
:Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation by inhibiting their ability to repair DNA damage. Here, we report a DNA repair suppressor, leucine-rich repeat-containing protein 31 (LRRC31), that was identified through a genome-wide CRISPR screen. We found that overexpression of LRRC31 suppresses DNA repair and sensitizes BCBMs to radiation. Mechanistically, LRRC31 interacts with Ku70/Ku80 and the ataxia telangiectasia mutated and RAD3-related (ATR) at the protein level, resulting in inhibition of DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) recruitment and activation, and disruption of the MutS homologue 2 (MSH2)-ATR module. We demonstrate that targeted delivery of the LRRC31 gene via nanoparticles improves the survival of tumour-bearing mice after irradiation. Collectively, our study suggests LRRC31 as a major DNA repair suppressor that can be targeted for cancer radiosensitizing therapy.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Chen Y,Jiang T,Zhang H,Gou X,Han C,Wang J,Chen AT,Ma J,Liu J,Chen Z,Jing X,Lei H,Wang Z,Bao Y,Baqri M,Zhu Y,Bindra RS,Hansen JE,Dou J,Huang C,Zhou Jdoi
10.1038/s41556-020-00586-6subject
Has Abstractpub_date
2020-10-01 00:00:00pages
1276-1285issue
10eissn
1465-7392issn
1476-4679pii
10.1038/s41556-020-00586-6journal_volume
22pub_type
杂志文章abstract：:The actin cable is a supracellular structure that embryonic epithelia produce to close gaps. However, the action of the cable remains debated. Here, we address the function of the cable using Drosophila dorsal closure, a paradigm to understand wound healing. First, we show that the actin cytoskeleton protein Zasp52 is...
journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2016-11-01 00:00:00
abstract：:Actin and myosin are major components of the cell cytoskeleton, with structural and regulatory functions that affect many essential cellular processes. Although they were traditionally thought to function only in the cytoplasm, it is now well accepted that actin and multiple myosins are found in the nucleus. Increasin...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
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更新日期：2011-11-02 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2008-05-01 00:00:00
abstract：:The precise regulation of growth factor signalling is crucial to the molecular control of development in Drosophila. Post-translational modification of signalling molecules is one of the mechanisms that modulate developmental signalling specificity. We describe a new gene, fringe connection (frc), that encodes a nucle...
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pub_type： 杂志文章
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更新日期：2018-07-01 00:00:00
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journal_title：Nature cell biology
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doi：10.1038/35023547
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2011-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1921
更新日期：2009-09-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2036
更新日期：2010-04-01 00:00:00
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doi：10.1038/ncb2151
更新日期：2011-02-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2260
更新日期：2011-06-19 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb975
更新日期：2003-05-01 00:00:00
abstract：:Many extracellular signals are transmitted to the interior of the cell by receptors with seven membrane-spanning helices that trigger their effects by means of heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins). These G-protein-coupled receptors (GPCRs) control various physiological functions i...
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journal_title：Nature cell biology
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doi：10.1038/35046510
更新日期：2000-12-01 00:00:00
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