Cancer Susceptibility and S Phase Initiation Sites
癌症易感性和 S 期起始位点
基本信息
- 批准号:7371150
- 负责人:
- 金额:$ 26.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-07-01 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:AffectAllelesArchitectureBindingCarcinogensCell CycleCellsChromosome abnormalityChromosomes, Human, Pair 1Chromosomes, Human, XClassComplexCpG IslandsDNADNA MethylationDNA RepairDNA SequenceDNA biosynthesisDNA replication forkDNA replication originDevelopmentDiploidyES Cell LineElementsEtiologyFailureFibroblastsFire - disastersG6PD geneGene ExpressionGene MutationGenesGeneticGenetic TranscriptionGenome MappingsGenomicsGlucosephosphate DehydrogenaseGoalsGrantHPRT1 geneHistonesHourHumanHuman GenomeHypoxanthine PhosphoribosyltransferaseKnowledgeLeadLinkLocalizedMalignant - descriptorMalignant NeoplasmsMapsModelingModificationMonitorMusMutationNeoplasmsNumbersOther FindingPhasePre-Replication ComplexPredispositionRecombinantsRegulationReplication OriginRepliconResearchResearch PersonnelRoleSequence DeletionSiteTestingThinkingTimeX Chromosomebasecancer cellcancer typecarcinogenesisgenetic elementhuman femaleimprintinsightprogramspromoterreplicator
项目摘要
DESCRIPTION (provided by applicant): Deletions and sequence mutations of genes are the mechanisms typically considered when evaluating the etiology and progression of neoplasia. This topic has been extensively examined over the past several decades. Likewise, genetic instability as manifested by development of numerical and structural alterations of chromosomes is also a typical feature of cancer development that has been the subject of intense study. More recently it has been recognized that many cancers manifest alterations in gene expression that are not coincident with gene mutations. These changes are thought to be associated with alterations of DNA methylation in the promoter of these genes and by histone modifications at the sites of these promoters. There have been far fewer efforts to identify the mechanisms that can explain these latter types of cancer-related changes. In this project we seek to understand mechanisms that can explain the transition of alleles of non-imprinted genes from synchronous to non-synchronous replication timing in carcinogenesis. While it is known that such shifts in replication timing can lead to the alterations in gene expression seen in many types of cancers, the exact mechanisms responsible for the conservation of replication timing are not known. Others and we found that both DNA replication and transcription are often initiated in or near the gene promoter and associated CpG island. In this project we seek to better define the essential genomic elements required for the function of DNA replication origins found at transcriptional promoters. We also pose the following questions: Do differences in origin firing times correspond to differences in the binding time of specific factors necessary for origin activation? Are there sites in normal human cells that slow or pause the progression of DNA replication forks? Are such sites involved in the regulation of the order of activation time of adjacent origins of DNA replication? To gain insights into these mechanisms and answer these questions we propose the following
Specific Aims. Specific Aim 1: Characterize genetic elements necessary for activity of the HPRT origin of replication.
Specific Aim 2: Analyze binding of the pre-replication complex at the HPRT and G6PD origins of replication on the active and the inactive X chromosome in female human cells.
Specific Aim 3: Analyze the architecture of replication and potential fork progression barriers in an early replicated region of the human genome.
描述(由申请人提供):基因缺失和序列突变是评估肿瘤的病因和进展时通常考虑的机制。在过去的几十年里,这个话题得到了广泛的研究。同样,染色体的数量和结构变化所表现出的遗传不稳定性也是癌症发展的典型特征,一直是密集研究的主题。最近,人们已经认识到,许多癌症表现出与基因突变不一致的基因表达变化。这些变化被认为与这些基因启动子中DNA甲基化的变化以及这些启动子上的组蛋白修饰有关。识别能够解释后一种癌症相关变化的机制的努力要少得多。在这个项目中,我们试图了解可以解释非印记基因的等位基因在致癌过程中从同步复制时间转换到非同步复制时间的机制。虽然已知复制时间的这种变化可以导致在许多类型的癌症中看到的基因表达的变化,但导致复制时间保持不变的确切机制尚不清楚。我们发现,DNA复制和转录通常都是在基因启动子和相关的CpG岛上或附近开始的。在这个项目中,我们试图更好地定义在转录启动子中发现的DNA复制起始点的功能所需的基本基因组元件。我们还提出了以下问题:起源激发时间的差异是否对应于起源激活所必需的特定因子的结合时间的差异?在正常的人类细胞中,是否存在减缓或暂停DNA复制分叉进程的位点?这些位点是否参与了DNA复制相邻起始点激活时间顺序的调节?为了深入了解这些机制并回答这些问题,我们提出了以下建议
明确的目标。具体目标1:确定HPRT复制起始点活性所需的遗传元件。
特定目的2:分析女性细胞中活跃和非活跃X染色体上HPRT和G6PD复制起始处的复制前复合体的结合。
具体目标3:分析人类基因组早期复制区域的复制架构和潜在的分叉进展障碍。
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 }}
David G. Kaufman其他文献
Differing effects of isoleucine deficiency on the toxicity of MNNG for 10T1/2 and CHO cells
- DOI:
10.1007/bf02616093 - 发表时间:
1978-06-01 - 期刊:
- 影响因子:1.900
- 作者:
Diane S. Greenberg;Joe W. Grisham;William N. Bell;Mary S. Baker;David G. Kaufman - 通讯作者:
David G. Kaufman
Analyses of carcinogen-modified oligonucleotides by fast atom bombardment/tandem mass spectrometry.
通过快原子轰击/串联质谱分析致癌物修饰的寡核苷酸。
- DOI:
10.1002/rcm.1290010409 - 发表时间:
1987 - 期刊:
- 影响因子:0
- 作者:
J. J. Dino;Christian R. Guenat;Kenneth B. Tomer;David G. Kaufman;R. Caprioli - 通讯作者:
R. Caprioli
Acute changes in the surface morphology of hamster tracheobronchial epithelium following benzo(a)pyrene and ferric oxide administration.
给予苯并(a)芘和氧化铁后仓鼠气管支气管上皮表面形态的急性变化。
- DOI:
- 发表时间:
1973 - 期刊:
- 影响因子:11.2
- 作者:
Curtis D. Port;Mary C. Henry;David G. Kaufman;David G. Kaufman;Curtis C. Harris;Kathleen V. Ketels - 通讯作者:
Kathleen V. Ketels
Sixth aspen cancer conference: Molecular mechanisms of genetic deregulation in toxicity and carcinogenesis
第六届白杨癌症会议:毒性和致癌作用中遗传失调的分子机制
- DOI:
- 发表时间:
1993 - 期刊:
- 影响因子:4.6
- 作者:
Raymond W. Tennant;C. C. Harris;David G. Kaufman;S. Nesnow;Thomas J. Slaga;Donald E. Stevenson;Benjamin F. Trump - 通讯作者:
Benjamin F. Trump
Quantitation by electron microscopy of the binding of highly specific antibodies to benzo[a]pyrene-DNA adducts.
通过电子显微镜对高度特异性抗体与苯并[a]芘-DNA 加合物的结合进行定量。
- DOI:
- 发表时间:
1985 - 期刊:
- 影响因子:4.7
- 作者:
R. Paules;Miriam C. Poirier;Marc J. Mass;S. H. Yuspa;David G. Kaufman - 通讯作者:
David G. Kaufman
David G. Kaufman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('David G. Kaufman', 18)}}的其他基金
Confocal Laser Scanning Microscope LSM 710 #5
共焦激光扫描显微镜 LSM 710
- 批准号:
7595557 - 财政年份:2009
- 资助金额:
$ 26.78万 - 项目类别:
Identification of Areas of Oxidative Damage in Human Genomic DNA
人类基因组 DNA 氧化损伤区域的鉴定
- 批准号:
7193167 - 财政年份:2007
- 资助金额:
$ 26.78万 - 项目类别:
FASEB Summer Conference on Nuclear Structure and Cancer
FASEB 核结构与癌症夏季会议
- 批准号:
7426335 - 财政年份:2007
- 资助金额:
$ 26.78万 - 项目类别:
Identification of Areas of Oxidative Damage in Human Genomic DNA
人类基因组 DNA 氧化损伤区域的鉴定
- 批准号:
7440180 - 财政年份:2007
- 资助金额:
$ 26.78万 - 项目类别:
Transformation of Human Endometrial Epithelial Cells
人子宫内膜上皮细胞的转化
- 批准号:
6868849 - 财政年份:2004
- 资助金额:
$ 26.78万 - 项目类别:
Transformation of Human Endometrial Epithelial Cells
人子宫内膜上皮细胞的转化
- 批准号:
6709781 - 财政年份:2004
- 资助金额:
$ 26.78万 - 项目类别:
Estrogens, Paracrine Factors, and Endometrial Cancer
雌激素、旁分泌因子和子宫内膜癌
- 批准号:
6612583 - 财政年份:2003
- 资助金额:
$ 26.78万 - 项目类别:
Estrogens, Paracrine Factors, and Endometrial Cancer
雌激素、旁分泌因子和子宫内膜癌
- 批准号:
7032997 - 财政年份:2003
- 资助金额:
$ 26.78万 - 项目类别:
Estrogens, Paracrine Factors, and Endometrial Cancer
雌激素、旁分泌因子和子宫内膜癌
- 批准号:
6888497 - 财政年份:2003
- 资助金额:
$ 26.78万 - 项目类别:
Estrogens, Paracrine Factors, and Endometrial Cancer
雌激素、旁分泌因子和子宫内膜癌
- 批准号:
6743952 - 财政年份:2003
- 资助金额:
$ 26.78万 - 项目类别:
相似海外基金
Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
- 批准号:
502556 - 财政年份:2024
- 资助金额:
$ 26.78万 - 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
- 批准号:
10659303 - 财政年份:2023
- 资助金额:
$ 26.78万 - 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
- 批准号:
10674405 - 财政年份:2023
- 资助金额:
$ 26.78万 - 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
- 批准号:
10758772 - 财政年份:2023
- 资助金额:
$ 26.78万 - 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
- 批准号:
10676499 - 财政年份:2023
- 资助金额:
$ 26.78万 - 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
- 批准号:
2748611 - 财政年份:2022
- 资助金额:
$ 26.78万 - 项目类别:
Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
- 批准号:
10532032 - 财政年份:2022
- 资助金额:
$ 26.78万 - 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
- 批准号:
22K05630 - 财政年份:2022
- 资助金额:
$ 26.78万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
- 批准号:
10525070 - 财政年份:2022
- 资助金额:
$ 26.78万 - 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
- 批准号:
10689017 - 财政年份:2022
- 资助金额:
$ 26.78万 - 项目类别: