DNA lesions involved in chemotherapy responses and their repair
化疗反应及其修复中涉及的 DNA 损伤
基本信息
- 批准号:nhmrc : 395500
- 负责人:
- 金额:$ 26.61万
- 依托单位:
- 依托单位国家:澳大利亚
- 项目类别:NHMRC Project Grants
- 财政年份:2006
- 资助国家:澳大利亚
- 起止时间:2006-01-01 至 2008-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The integrity of the human genome is constantly threatened by spontaneous DNA damage from products of normal metabolism, for example DNA oxidation, or environmental mutagens and carcinogens such as UV light. Improperly repaired DNA damage is a major contributing factor to the onset of cancer. To prevent this, human cells have a multitude of specialised DNA repair mechanisms to repair distinct lesions in the best possible way. As a consequence, mutations in DNA repair genes lead to increased cancer risk. Common examples for cancer-associated DNA repair gene mutations include the BRCA1 and BRCA2 breast cancer genes, and the MLH1 gene mutated in familial non-polyposis colorectal cancer. We have identified a novel human DNA repair protein termed ASCIZ that performs a function similar to BRCA1 and BRCA2 in that it regulates the concentration of the RAD51 repair protein in specific DNA repair centres in the cell nucleus. However, compared to BRCA1-BRCA2, ASCIZ performs this function in response to different types of DNA damage and acts in concert with the MLH1 protein. Here we want to investigate what the specific DNA lesions are that are repaired by ASCIZ, and we want to determine if the repair involves a copy mechanism that utilises intact genes as repair templates. In addition, we want to generate animals in which the ASCIZ gene is mutated, as a model to study its role in cancer development in humans. Cells that lack ASCIZ are dramatically hypersensitive to DNA damaging agents that are similar to clinically used chemotherapy drugs. We hope that our studies may identify possible approaches to develop drugs against ASCIZ and related proteins in order to kill cancer cells more efficiently.
人类基因组的完整性不断受到正常代谢产物(例如 DNA 氧化)或环境诱变剂和致癌物(例如紫外线)造成的自发 DNA 损伤的威胁。 DNA 损伤修复不当是癌症发生的一个主要因素。为了防止这种情况发生,人类细胞拥有多种专门的 DNA 修复机制,以尽可能最好的方式修复不同的损伤。因此,DNA 修复基因的突变会导致癌症风险增加。癌症相关 DNA 修复基因突变的常见例子包括 BRCA1 和 BRCA2 乳腺癌基因,以及家族性非息肉病性结直肠癌中突变的 MLH1 基因。我们发现了一种名为 ASCIZ 的新型人类 DNA 修复蛋白,其功能与 BRCA1 和 BRCA2 类似,可调节细胞核中特定 DNA 修复中心的 RAD51 修复蛋白浓度。然而,与 BRCA1-BRCA2 相比,ASCIZ 响应不同类型的 DNA 损伤而发挥此功能,并与 MLH1 蛋白协同作用。在这里,我们想要研究 ASCIZ 修复的特定 DNA 损伤是什么,并且我们想要确定修复是否涉及利用完整基因作为修复模板的复制机制。此外,我们希望培育出 ASCIZ 基因突变的动物,作为研究其在人类癌症发展中的作用的模型。缺乏 ASCIZ 的细胞对类似于临床使用的化疗药物的 DNA 损伤剂非常敏感。我们希望我们的研究能够找到开发针对 ASCIZ 和相关蛋白的药物的可能方法,以便更有效地杀死癌细胞。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
A/Pr Jorg Heierhorst其他文献
A/Pr Jorg Heierhorst的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('A/Pr Jorg Heierhorst', 18)}}的其他基金
A tumour suppressor pathway that removes DNA-RNA hybrids
消除 DNA-RNA 杂交体的肿瘤抑制途径
- 批准号:
nhmrc : GNT1139099 - 财政年份:2018
- 资助金额:
$ 26.61万 - 项目类别:
Project Grants
A tumour suppressor pathway that removes DNA-RNA hybrids
消除 DNA-RNA 杂交体的肿瘤抑制途径
- 批准号:
nhmrc : 1139099 - 财政年份:2018
- 资助金额:
$ 26.61万 - 项目类别:
Project Grants
Regulation and function of the Zinc-finger protein ASCIZ in the DNA damage response
锌指蛋白 ASCIZ 在 DNA 损伤反应中的调节和功能
- 批准号:
nhmrc : 1026125 - 财政年份:2012
- 资助金额:
$ 26.61万 - 项目类别:
Project Grants
Multi-domain regulation of DNA damage response kinases
DNA 损伤反应激酶的多域调控
- 批准号:
nhmrc : 1009764 - 财政年份:2011
- 资助金额:
$ 26.61万 - 项目类别:
NHMRC Project Grants
Developmental functions of a novel Zinc-finger protein
新型锌指蛋白的发育功能
- 批准号:
nhmrc : 1009763 - 财政年份:2011
- 资助金额:
$ 26.61万 - 项目类别:
NHMRC Project Grants
Functions of ASCIZ in the repair of accidental and programmed DNA base damage
ASCIZ 在修复意外和程序性 DNA 碱基损伤中的功能
- 批准号:
nhmrc : 559020 - 财政年份:2009
- 资助金额:
$ 26.61万 - 项目类别:
NHMRC Project Grants
Identification of telomere-specific recombination pathways
端粒特异性重组途径的鉴定
- 批准号:
nhmrc : 502600 - 财政年份:2008
- 资助金额:
$ 26.61万 - 项目类别:
NHMRC Project Grants
Research Fellowship - Grant ID:448302
研究奖学金 - 拨款 ID:448302
- 批准号:
nhmrc : 448302 - 财政年份:2007
- 资助金额:
$ 26.61万 - 项目类别:
NHMRC Research Fellowships
Regulation and assembly of nuclear DNA repair centres
核DNA修复中心的调控和组装
- 批准号:
nhmrc : 395501 - 财政年份:2006
- 资助金额:
$ 26.61万 - 项目类别:
NHMRC Project Grants
相似国自然基金
脂滴聚集型小胶质细胞介导的髓鞘病变促进小鼠抑郁样行为及其机制研究
- 批准号:82371528
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
相似海外基金
A randomized, sham-controlled clinical trial evaluating individualized neuromodulation of cortical regions involved in neurogenic overactive bladder in Multiple Sclerosis
一项随机、假对照临床试验,评估多发性硬化症患者神经源性膀胱过度活动症相关皮质区域的个体化神经调节
- 批准号:
10560461 - 财政年份:2023
- 资助金额:
$ 26.61万 - 项目类别:
Identification of miRNAs involved in the premalignant lesions in gastrointestinal tract and their malignant transformation
胃肠道癌前病变及其恶性转化相关miRNA的鉴定
- 批准号:
19K17483 - 财政年份:2019
- 资助金额:
$ 26.61万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Identification of molecules involved in the carcinogenesis of serrated lesions of the colon and their clinical application.
结肠锯齿状病变癌变相关分子的鉴定及其临床应用。
- 批准号:
19K17437 - 财政年份:2019
- 资助金额:
$ 26.61万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Morecular pathology involved in phenotypic expression and morphological chenges in jaw lesions
颌骨病变表型表达和形态变化涉及的血管病理学
- 批准号:
15K20571 - 财政年份:2015
- 资助金额:
$ 26.61万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Zinc finger proteins involved in neuronal development
锌指蛋白参与神经元发育
- 批准号:
8127080 - 财政年份:2011
- 资助金额:
$ 26.61万 - 项目类别:
Zinc finger proteins involved in neuronal development
锌指蛋白参与神经元发育
- 批准号:
8367856 - 财政年份:2011
- 资助金额:
$ 26.61万 - 项目类别:
Zinc finger proteins involved in neuronal development
锌指蛋白参与神经元发育
- 批准号:
8501705 - 财政年份:2011
- 资助金额:
$ 26.61万 - 项目类别:
Identification of factors that involved in migration of mesenchymal stem cells to lesions of neurodegenerative diseases
鉴定参与间充质干细胞向神经退行性疾病病变迁移的因素
- 批准号:
23658233 - 财政年份:2011
- 资助金额:
$ 26.61万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Identification of the responsible genes on 8p involved in themalignant transformation of the precancerous lesions in the pancreas .
鉴定8p上参与胰腺癌前病变恶变的相关基因。
- 批准号:
22590335 - 财政年份:2010
- 资助金额:
$ 26.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification and functional characterization of novel genes involved in the formation of osteoblastic bone lesions in advanced prostate cancer
参与晚期前列腺癌成骨细胞骨病变形成的新基因的鉴定和功能表征
- 批准号:
332973-2006 - 财政年份:2006
- 资助金额:
$ 26.61万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's