Search

Search

このページは機械翻訳されています。他のページは英語で表示される場合があります。 View in English

ホーム
...
研究分野生物医学と臨床科学腫瘍学とがん発生分子標的
核cGASはDNA修復を抑制し,腫瘍発生を促進する.

核cGASはDNA修復を抑制し,腫瘍発生を促進する.

Haipeng Liu ^1,2, Haiping Zhang ³, Xiangyang Wu ^1,2, Dapeng Ma ², Juehui Wu ^1,2, Lin Wang ^1,2, Yan Jiang ², Yiyan Fei ⁴, Chenggang Zhu ⁴, Rong Tan ⁵, Peter Jungblut ⁶, Gang Pei ⁷, Anca Dorhoi ^7,8, Qiaoling Yan ², Fan Zhang ⁹, Ruijuan Zheng ¹, Siyu Liu ², Haijiao Liang ^1,2, Zhonghua Liu ¹, Hua Yang ¹, Jianxia Chen ^1,2, Peng Wang ², Tianqi Tang ², Wenxia Peng ², Zhangsen Hu ³, Zhu Xu ³, Xiaochen Huang ¹, Jie Wang ¹, Haohao Li ¹, Yilong Zhou ^1,2, Feng Liu ¹, Dapeng Yan ¹⁰, Stefan H E Kaufmann ⁷, Chang Chen ⁹, Zhiyong Mao ¹¹, Baoxue Ge ^12,13

Haipeng Liu ^1,2, Haiping Zhang ³, Xiangyang Wu ^1,2

¹Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
²Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
³Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁴Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai, China.
⁵Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China.
⁶Protein Purification Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany.
⁷Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
⁸Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald Insel Riems, Germany.
⁹Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
¹⁰Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai, China.
¹¹Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. zhiyong_mao@tongji.edu.cn.
¹²Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. baoxue_ge@tongji.edu.cn.
¹³Clinical Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. baoxue_ge@tongji.edu.cn.

⁰Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Nature +

|

2018年10月26日

関連する実験動画

These videos have been matched automatically. Contact us if they are not relevant.

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

See all related videos

PubMedで要約を見る

まとめ

この要約は機械生成です。

サイクルGMP- AMP合成酵素 (cGAS) は,同種の再結合を抑制することによってDNA修復を抑制する. cGASを阻害すると DNAの損傷と腫瘍の成長が減り癌治療のターゲットとして示唆されます

科学分野

分子生物学
免疫学
癌研究

背景

ホモログ的再結合は DNAの二重鎖の断裂を修復しゲノムの安定性を維持し癌を予防します
サイクルGMP-AMP合成酵素 (cGAS) は,先天的な免疫に不可欠な細胞塩基DNAセンサーである.
DNA修復経路におけるcGASの役割は以前は知られていなかった.

研究の目的

DNA修復におけるcGASの役割,特に同種の再結合を調査する.
cGASがDNA修復に影響を与えるメカニズムを解明する.
ガンにおけるcGASの治療の可能性を評価する.

主な方法

マウスとヒトの細胞におけるDNA損傷に対するcGASの局所化と機能を調査した.
cGAS核転移とリン酸化を研究するためにインポートリンαとBリンパチロシンキナーゼ (BLK) を利用した.
cGAS,PARP1,およびPARP1-Timeless複合体の間の相互作用をDNAの二重鎖の断裂で調べました.
cGASのDNA損傷と腫瘍の成長に対するインパクトをin vitroとin vivoで評価した.

主要な成果

cGASの核転移を誘発するDNA損傷は,インポートリンαとBLK媒介のリン酸化によって促進される.
核のcGASはPARP1と相互作用し,PARP1-Timeless複合体を破壊し,同種の再結合を抑制する.
cGASの破壊はDNAの損傷を大幅に減らし,腫瘍の成長を阻害する.

結論

核cGASは同種の再結合媒介DNA修復の抑制剤として作用する.
cGASは重要なDNA修復メカニズムを阻害することで腫瘍の成長を促します.
cGASをターゲットにすることで癌の予防と治療に有望な戦略が生まれます

関連する実験動画

自動的に一致したビデオです Contact us もしそれらが関連していない場合

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

See all related videos

関連する概念動画

Overview of DNA Repair

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...

Overview of DNA Repair

Overview of DNA Repair

Base-pairing and DNA Repair

Base-pairing and DNA Repair

Mismatch Repair

Mismatch Repair

Overview

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.

The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair

The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount...

Long-patch Base Excision Repair

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:

Lesion type: Depending on the type of base damage, a specific DNA glycosylase - mono or bifunctional, is recruited to the damaged site. While the sequential action of a monofunctional glycosylase favors long patch repair...

Non-nuclear Inheritance

Non-nuclear Inheritance

Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm⁠—such as chloroplasts and mitochondria⁠—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.

Mitochondria are present in both plants and animal cells. They are regarded as the “powerhouses” of eukaryotic...

Share

X
Facebook
LinkedIn
YouTube

ABOUT JoVE

Overview
Leadership
Blog
JoVE Help Center

AUTHORS

Publishing Process
Editorial Board
Scope & Policies
Peer Review
FAQ
Submit

LIBRARIANS

Testimonials
Subscriptions
Access
Resources
Library Advisory Board
FAQ

RESEARCH

JoVE Journal
Methods Collections
JoVE Encyclopedia of Experiments
Archive

EDUCATION

JoVE Core
JoVE Business
JoVE Science Education
JoVE Lab Manual
Faculty Resource Center
Faculty Site

Terms & Conditions of Use
Privacy Policy
Policies