Regulation of Initial Steps of Chromosomal Breaks Repair
染色体断裂修复初始步骤的调控
基本信息
- 批准号:10611707
- 负责人:
- 金额:$ 6.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-01-01 至 2026-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAgingAnimal ModelAntibodiesBiological AssayCell CycleCellsChromatinChromosomal BreaksChromosomal StabilityComplexDNADNA Double Strand BreakDiseaseDouble Strand Break RepairEuchromatinExcisionFission YeastGene TargetingGenetic RecombinationGenetic TranscriptionGenome StabilityGoalsHeterochromatinHumanMalignant NeoplasmsMediatingMedicalMinorNonhomologous DNA End JoiningPathway interactionsProcessProteinsRAD52 geneRegulationRoleSingle-Stranded DNASystemYeastsdesignhelicasehomologous recombinationnucleaserepairedresponse
项目摘要
Recombination is essential in maintaining genome stability, and even minor deficiency in
recombinational double-strand break (DSB) repair pathways results in cancer or other severe
diseases. The initial processing of DNA DSBs to single strands, a process termed DNA end
resection, is the critical first step of homologous recombination needed for the loading of damage
response and repair proteins. Resection is tightly controlled in the cell cycle and determines the
usage of homologous recombination versus nonhomologous end joining for repair. In yeast and
human cells, the Mre11-Rad50-Nbs1/Xrs2 complex initiates resection, whereas Exo1 or Sgs1-
Dna2 mediates extensive resection. Systematic studies of resection have thus far only been done
in euchromatin, whereas we propose to study it in three different types of silenced
heterochromatin. We designed many new assays to examine resection within transcriptionally
silent chromatin in fission yeast (Aim #1). The fission yeast system provides an excellent model
organism for this study as chromatin features are well conserved with those in human cells. In
Aim #2 we focus on control of one of the most mutagenic pathways of DSB repair called Break
Induced Replication (BIR). BIR is normally used for the repair of a single-end DSB. Here the goal
is to understand how this pathway is suppressed during the repair of two-ended DSBs. We focus
on the role of ssDNA annealing by Rad52 and synchronous resection of two ends of a DSB by
the Mre11-Rad50-Xrs2 complex. In Aim #3 we focus on the resection-independent function of
Dna2 nuclease/helicase during homologous recombination.
重组对维持基因组的稳定性至关重要,即使是微小的缺陷
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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{{ truncateString('Grzegorz A Ira', 18)}}的其他基金
Regulation of Initial Steps of Chromosomal Breaks Repair
染色体断裂修复初始步骤的调控
- 批准号:
10364268 - 财政年份:2018
- 资助金额:
$ 6.91万 - 项目类别:
Regulation of Initial Steps of Chromosomal Breaks Repair
染色体断裂修复初始步骤的调控
- 批准号:
10554415 - 财政年份:2018
- 资助金额:
$ 6.91万 - 项目类别:
Regulation of DNA recombination in Saccharomyces cerevisiae
酿酒酵母 DNA 重组的调控
- 批准号:
7896066 - 财政年份:2009
- 资助金额:
$ 6.91万 - 项目类别:
Mechanism and Regulation of DNA recombination in Saccharomyces cerevisiae
酿酒酵母DNA重组机制及调控
- 批准号:
9912782 - 财政年份:2007
- 资助金额:
$ 6.91万 - 项目类别:
Regulation of DNA recombination in Saccharomyces cerevisiae
酿酒酵母 DNA 重组的调控
- 批准号:
7809626 - 财政年份:2007
- 资助金额:
$ 6.91万 - 项目类别:
MECHANISM AND REGULATION OF DNA RECOMBINATION IN SACCHAROMYCES CEREVISIAE
酿酒酵母DNA重组的机制和调控
- 批准号:
10209684 - 财政年份:2007
- 资助金额:
$ 6.91万 - 项目类别:
Regulation of DNA recombination in Saccharomyces cerevisiae
酿酒酵母 DNA 重组的调控
- 批准号:
7245956 - 财政年份:2007
- 资助金额:
$ 6.91万 - 项目类别:
Regulation of DNA recombination in Saccharomyces cerevisiae
酿酒酵母 DNA 重组的调控
- 批准号:
7413253 - 财政年份:2007
- 资助金额:
$ 6.91万 - 项目类别:
Regulation of DNA recombination in Saccharomyces cerevisiae
酿酒酵母 DNA 重组的调控
- 批准号:
8667465 - 财政年份:2007
- 资助金额:
$ 6.91万 - 项目类别:
Mechanism and Regulation of DNA recombination in Saccharomyces cerevisiae
酿酒酵母DNA重组机制及调控
- 批准号:
9236365 - 财政年份:2007
- 资助金额:
$ 6.91万 - 项目类别:
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