A Novel Protein Complex Controls Homologous Recombination Repair in Breast Cancer
一种新型蛋白质复合物控制乳腺癌的同源重组修复
基本信息
- 批准号:9139419
- 负责人:
- 金额:$ 16.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-30 至 2018-08-31
- 项目状态:已结题
- 来源:
- 关键词:Affinity ChromatographyBRCA1 geneBRCA2 geneBindingBinding ProteinsBioinformaticsBreast Cancer CellBreast Cancer PatientBreast Cancer PreventionBreast Cancer TreatmentBreast Cancer cell lineCamptothecinCancer EtiologyCancer PatientCancer-Predisposing GeneCell CycleCellsCisplatinClinical ManagementComplexDNADNA DamageDNA Double Strand BreakDNA RepairDNA Repair PathwayDataDefectDevelopmentDiagnosisG2 PhaseGenesGenomic InstabilityGoalsHealthHereditary Breast CarcinomaHumanIncidenceIonizing radiationKnockout MiceKnowledgeLeadMalignant NeoplasmsMolecularMusMutateMutationNamesNonsense MutationPathway interactionsPharmaceutical PreparationsPlayPrevention strategyProcessProteinsRad51 recombinaseRecruitment ActivityRegimenResearchRisk FactorsRoleS PhaseSamplingSister ChromatidSiteTP53 geneTestingTherapeuticTissue SampleTranslationsTumor Suppressor Proteinscancer therapychemotherapyclinical practicedesigndrug sensitivityexome sequencinghomologous recombinationimprovedin vivoinhibitor/antagonistmalignant breast neoplasmmortalitynovelnovel anticancer drugprotein complexrecombinaserecombinational repairrepairedresearch studyresponsetherapy developmenttumortumorigenesis
项目摘要
DESCRIPTION (provided by applicant): Inheritance of mutations in one of the breast cancer susceptibility genes, BRCA1 or BRCA2, is the most significant risk factor for developing breast cancer. BRCA1 and BRCA2 are known to function in a common DNA repair pathway, named homologous recombination (HR). HR is an essential DNA repair process that uses the homologous sister chromatid to carry out accurate repair of DNA double-strand breaks (DSBs), predominantly taking place during S and G2 phases of the cell cycle. However, while BRCA1 and BRCA2 are frequently mutated in familial breast cancers, mutations of these tumor suppressors are rare in sporadic breast cancers, raising the possibility that other genes involved in HR repair pathway, but not BRCA1 or BRCA2, may be mutated or dysregulated in sporadic breast cancers. In fact, HR deficiencies are frequently present in sporadic breast cancers (defined as a BRCAness or BRCA-like profile). To better understand the function of HR defects in sporadic breast cancer development, we have to know more about HR pathway by identifying novel HR factors other than the known BRCA1 and BRCA2 tumor suppressors. The BRCA2-interacting protein, RAD51, is at the center of HR pathway. This proposed project focuses on identifying a set of new RAD51-associated HR factors, including FIGNL1, KIAA0146 and C1orf112, and testing their potential roles in breast cancer development and treatment. The specific aims are: Aim 1: Elucidate the molecular functions of FIGNL1 protein complex in HR repair; Aim 2: Evaluate the functions of FIGNL1 in tumorigenesis; Aim 3: Determine the potential roles of FIGNL1 protein complex in breast cancer development and therapy. The proposed study is expected to identify novel factors involved in HR repair and generate important knowledge for understanding breast cancer etiology, which may have great implications for the clinical management of breast cancer patients.
描述(由申请人提供):在乳腺癌易感性基因之一BRCA1或BRCA2中突变的遗传是发展乳腺癌的最重要危险因素。已知BRCA1和BRCA2在常见的DNA修复途径中起作用,称为同源重组(HR)。 HR是一个必不可少的DNA修复过程,它使用同源姐妹染色单体对DNA双链断裂(DSB)进行准确的修复,主要发生在细胞周期的S和G2阶段。但是,尽管BRCA1和BRCA2经常在家族性乳腺癌中突变,但这些肿瘤抑制剂的突变在零星的乳腺癌中很少见,从而增加了与HR修复途径相关的其他基因,但可能不涉及BRCA1或BRCA2,但可能会突变或失调零星的乳腺癌。实际上,人力资源缺陷经常存在于零星的乳腺癌中(定义为BRCANESS或类似BRCA的轮廓)。为了更好地了解人力资源缺陷在散发性乳腺癌发展中的功能,我们必须通过鉴定已知的BRCA1和BRCA2肿瘤抑制子以外的其他新的HR因子来了解有关HR途径的更多信息。 BRCA2相互作用蛋白RAD51在HR途径的中心。该拟议的项目着重于确定一组新的Rad51相关的HR因子,包括Fignl1,Kiaa0146和C1orf112,并测试其在乳腺癌发育和治疗中的潜在作用。具体目的是:目标1:阐明HR修复中Fignl1蛋白复合物的分子功能; AIM 2:评估Fignl1在肿瘤发生中的功能; AIM 3:确定Fignl1蛋白复合物在乳腺癌发育和治疗中的潜在作用。拟议的研究预计将确定涉及人力资源修复的新因素,并为了解乳腺癌病因而产生重要的知识,这可能对乳腺癌患者的临床管理具有很大的影响。
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 }}
Jingsong Yuan其他文献
Jingsong Yuan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('Jingsong Yuan', 18)}}的其他基金
A Novel Protein Complex Controls Homologous Recombination Repair in Breast Cancer
一种新型蛋白质复合物控制乳腺癌的同源重组修复
- 批准号:
8700611 - 财政年份:2015
- 资助金额:
$ 16.2万 - 项目类别:
A Novel Protein Complex Controls Homologous Recombination Repair in Breast Cancer
一种新型蛋白质复合物控制乳腺癌的同源重组修复
- 批准号:
9324884 - 财政年份:2015
- 资助金额:
$ 16.2万 - 项目类别:
相似国自然基金
调控BRCA1突变乳腺癌PARP抑制剂应答的关键增强子及其下游基因研究
- 批准号:
- 批准年份:2023
- 资助金额:220 万元
- 项目类别:
BRCA1/2基因不同突变位点对对侧乳腺癌发病风险的差异影响及其机制探索
- 批准号:82372717
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
BRCA1单倍剂量不足效应诱导产生的机制及其与基因组不稳定和杂合突变致癌的联系
- 批准号:
- 批准年份:2021
- 资助金额:54.7 万元
- 项目类别:面上项目
巨噬细胞通过外泌体/XRN1通路降解胰腺导管上皮细胞BRCA1/2 mRNA引发基因组不稳定的机制
- 批准号:81873587
- 批准年份:2018
- 资助金额:57.0 万元
- 项目类别:面上项目
FAM35A-C20orf196复合物在DSB修复通路选择调控中的功能研究
- 批准号:31870807
- 批准年份:2018
- 资助金额:59.0 万元
- 项目类别:面上项目
相似海外基金
Synergize a novel homologous recombination inhibitor with DNA damagingagents in TNBC
在 TNBC 中协同新型同源重组抑制剂与 DNA 损伤剂
- 批准号:
10760604 - 财政年份:2023
- 资助金额:
$ 16.2万 - 项目类别:
A Novel Protein Complex Controls Homologous Recombination Repair in Breast Cancer
一种新型蛋白质复合物控制乳腺癌的同源重组修复
- 批准号:
8700611 - 财政年份:2015
- 资助金额:
$ 16.2万 - 项目类别:
A Novel Protein Complex Controls Homologous Recombination Repair in Breast Cancer
一种新型蛋白质复合物控制乳腺癌的同源重组修复
- 批准号:
9324884 - 财政年份:2015
- 资助金额:
$ 16.2万 - 项目类别:
Molecular Mechanisms of BRCA1-Dependent DNA Damage Response and Tumorogenesis
BRCA1 依赖性 DNA 损伤反应和肿瘤发生的分子机制
- 批准号:
9269160 - 财政年份:2008
- 资助金额:
$ 16.2万 - 项目类别:
Molecular Mechanisms of BRCA1-Dependent DNA Damage Response and Tumorogenesis
BRCA1 依赖性 DNA 损伤反应和肿瘤发生的分子机制
- 批准号:
9079407 - 财政年份:2008
- 资助金额:
$ 16.2万 - 项目类别: