Origin firing at repetitive sequences and genome replication

重复序列和基因组复制的起源

基本信息

  • 批准号:
    9008959
  • 负责人:
  • 金额:
    $ 47.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-02-01 至 2019-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant) Over half of the human genome is comprised of repetitive DNA organized as gene-poor, late replicating, transcriptionally silent heterochromatin. Recent studies suggest that there is a widespread opening of chromatin at repeated regions during carcinogenesis and aging. Given the total amount of repetitive DNA and the tendency of sequences in open chromatin to more readily serve as replication origins, these chromatin changes could significantly perturb global genome replication by outcompeting other regions of the genome for limiting replication factors. Indeed, our data from budding yeast suggest that increasing the efficiency of origin firing at repetitive sequences impairs DNA replication across the genome. In this proposal we use Saccharomyces cerevisiae to test our model that nucleosome re-positioning promotes the recruitment of initiation factors to replication origins in repetitive sequences and furthermore, that activation of origins in these repetitive sequences compromises the replication and stability of unique portions of the genome. S. cerevisiae is an excellent system in which to perform these tests: the major repetitive sequence, the ribosomal DNA (rDNA) is composed of homogenous tandem repeats (150 copies), each containing a potential origin of replication whose function is sensitive to chromatin context. Moreover, the sequence specificity of yeast origins creates uniform and predictable positioning of replication initiation factors and nucleosomes in their vicinity, greatly facilitating application and interpretation of a deep sequencing method for epigenomic profiling that we have developed. Our results will provide insights into the mechanisms by which chromatin and nucleosome positioning modulate replication origins at repetitive sequences and will shed light on the largely unexplored phenomenon of intra-genomic competition for replication resources as a mechanism that shapes global replication.
DESCRIPTION(由申请人提供)

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)

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Antonio Bedalov其他文献

Antonio Bedalov的其他文献

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{{ truncateString('Antonio Bedalov', 18)}}的其他基金

MeCP2 reactivation from the inactive X chromosome as treatment for Rett syndrome
从失活的 X 染色体重新激活 MeCP2 作为雷特综合征的治疗方法
  • 批准号:
    10826905
  • 财政年份:
    2023
  • 资助金额:
    $ 47.23万
  • 项目类别:
Origin firing at repetitive sequences and genome replication
重复序列和基因组复制的起源
  • 批准号:
    10356149
  • 财政年份:
    2016
  • 资助金额:
    $ 47.23万
  • 项目类别:
Origin firing at repetitive sequences and genome replication - Admin Supplement
重复序列和基因组复制的起源 - 管理补充
  • 批准号:
    10626663
  • 财政年份:
    2016
  • 资助金额:
    $ 47.23万
  • 项目类别:
Origin firing at repetitive sequences and genome replication
重复序列和基因组复制的起源
  • 批准号:
    10651624
  • 财政年份:
    2016
  • 资助金额:
    $ 47.23万
  • 项目类别:
SIRT2 Inhibitors for the Treatment of B-cell Lymphoma
SIRT2 抑制剂用于治疗 B 细胞淋巴瘤
  • 批准号:
    9197069
  • 财政年份:
    2016
  • 资助金额:
    $ 47.23万
  • 项目类别:
SIRT2 Inhibitors for the Treatment of B-cell Lymphoma
SIRT2 抑制剂用于治疗 B 细胞淋巴瘤
  • 批准号:
    10602858
  • 财政年份:
    2016
  • 资助金额:
    $ 47.23万
  • 项目类别:
Protein Biomarkers in Childhood Acute Myeloid Leukemia
儿童急性髓系白血病的蛋白质生物标志物
  • 批准号:
    8227276
  • 财政年份:
    2012
  • 资助金额:
    $ 47.23万
  • 项目类别:
Protein Biomarkers in Childhood Acute Myeloid Leukemia
儿童急性髓系白血病的蛋白质生物标志物
  • 批准号:
    8435374
  • 财政年份:
    2012
  • 资助金额:
    $ 47.23万
  • 项目类别:
Development of cambinol analogues as antilymphoma agents
作为抗淋巴瘤药物的 Cambinol 类似物的开发
  • 批准号:
    7768411
  • 财政年份:
    2008
  • 资助金额:
    $ 47.23万
  • 项目类别:
Development of cambinol analogues as antilymphoma agents
作为抗淋巴瘤药物的 Cambinol 类似物的开发
  • 批准号:
    8230766
  • 财政年份:
    2008
  • 资助金额:
    $ 47.23万
  • 项目类别:

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激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
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