Single Stranded DNA: The Genome's Achilles Heel
Single Stranded DNA: The Genome's Achilles Heel
批准号:
8392278
负责人:
WENYI FENG
金额:
$21.28万
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-07-30 至 2014-11-30
关键词:
Chromosome BreakageChromosome Fragile SitesComplexCoupledDNA DamageDNA biosynthesisDefectDiseaseEventGelGenerationsGenetic MaterialsGenetic ScreeningGenomeGenomic InstabilityHumanHuman GenomeLeadLinkMalignant NeoplasmsMapsMass Spectrum AnalysisMutationNormal CellOrganismOther GeneticsProcessProductionReagentReplication OriginReplication-Associated ProcessResearchRoleSingle-Stranded DNASiteStressSystemTechniquesTestingYeastsgenome-widehuman diseaseinterestmutantnucleaseprevent
中文摘要
DNA复制是一个基本的过程,所有生物体都依赖于它来忠实地传递遗传信息。
从一代到下一代的材料。DNA复制过程通常会受到以下因素的"压力":
突变或外源性试剂可导致DNA损伤或复制障碍
机械.复制应激可引起基因组不稳定性,并可能最终导致疾病
包括癌症我的主要研究兴趣是缺陷复制如何导致基因组不稳定性。的
控制这一提议的一般假设是,复制时单链DNA(ssDNA)的产生
在复制检查点缺陷突变体中,分叉停滞和不稳定是潜在的致命事件,
阻止基因组的完全合成,导致染色体断裂,最终导致基因组
不稳定
该项目的具体目标是:
1.研究复制应激过程中大量ssDNA形成与染色体之间的联系
使用全基因组ssDNA和染色体断裂作图技术,
申请人结合其他遗传方法。
2.通过检查,阐明HU中检查点突变体中复制叉不稳定性的机制/原因
在微型染色体复制应激时复制复合物中发生的结构/组成变化
纯化系统与质谱联用。
3.使用ssDNA和DNA片段的组合鉴定人类的复制起点和染色体脆性位点。
染色体断裂作图,已经适用于哺乳动物系统。
英文摘要
DNA replication is a fundamental process on which all organisms depend for faithful passage of genetic
material from one generation to the next. The DNA replication process is often "stressed" either by
mutations or by exogenous reagents that can cause DNA damage or impediments to the replication
machinery. Replication stress can give rise to genomic instability and may ultimately lead to diseases
including cancer. My main research interest is how defective replication cause genomic instability. The
general hypothesis governing this proposal is that single-stranded DNA (ssDNA) production upon replication
fork stalling and destablization in replication checkpoint-deficient mutants is a potentially lethal event that
prevents complete synthesis of the genome, causes chromosomal breakage, and ultimately genomic
instability.
The specific aims of this project are:
1. Investigate the link between extensive ssDNA formation during replication stress and chromosome
breakage using the genome-wide ssDNA and chromosome breakage mapping techniques developed by the
applicant in combination with other genetic approaches.
2. Elucidate the mechanism/cause of replication fork instability in checkpoint mutants in HU by examining
the structural/compositional changes that occur in the replication complex upon replication stress by a minichromosome
purification system coupled with mass spectrometry.
3. Identify origins of replication and chromosome fragile sites in humans using a combination of ssDNA and
chromosome breakage mapping that have been adapted for the mammalian systems.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1093/nar/gkw720
发表时间:
2016-12-01
期刊:
Nucleic acids research
影响因子:
14.9
作者:
[Peng J, Feng W]
通讯作者:
Feng W
DOI:
10.1101/gr.180497.114
发表时间:
2015-03
期刊:
Genome research
影响因子:
7
作者:
[Hoffman EA, McCulley A, Haarer B, Arnak R, Feng W]
通讯作者:
Feng W
DOI:
10.1534/g3.113.009100
发表时间:
2014-01-10
期刊:
G3 (Bethesda, Md.)
影响因子:
--
作者:
[McCulley A, Haarer B, Viggiano S, Karchin J, Feng W]
通讯作者:
Feng W
Understanding the Genome Maintenance Function of the Fragile X Protein (FMRP)
-
批准号:10511129
-
项目类别:
-
资助金额:$24.45万
-
财政年份:2022
-
负责人:WENYI FENG
-
依托单位:
Understanding the Genome Maintenance Function of the Fragile X Protein (FMRP)
-
批准号:10661830
-
项目类别:
-
资助金额:$20.38万
-
财政年份:2022
-
负责人:WENYI FENG
-
依托单位:
Mechanisms of replication stress-induced chromosome fragility
-
批准号:9193425
-
项目类别:
-
资助金额:$32.4万
-
财政年份:2016
-
负责人:WENYI FENG
-
依托单位:
Single Stranded DNA: The Genome's Achilles Heel
-
批准号:7882988
-
项目类别:
-
资助金额:$7.32万
-
财政年份:2009
-
负责人:WENYI FENG
-
依托单位:
Single Stranded DNA: The Genome's Achilles Heel
-
批准号:7477136
-
项目类别:
-
资助金额:$8.85万
-
财政年份:2007
-
负责人:WENYI FENG
-
依托单位:
Single Stranded DNA: The Genome's Achilles Heel
-
批准号:8188793
-
项目类别:
-
资助金额:$22.22万
-
财政年份:2007
-
负责人:WENYI FENG
-
依托单位:
Single Stranded DNA: The Genome's Achilles Heel
-
批准号:7299315
-
项目类别:
-
资助金额:$8.66万
-
财政年份:2007
-
负责人:WENYI FENG
-
依托单位:
Single Stranded DNA: The Genome's Achilles Heel
-
批准号:8204426
-
项目类别:
-
资助金额:$22.33万
-
财政年份:2007
-
负责人:WENYI FENG
-
依托单位:
Investigating of a Novel Checkpoint in S. Cerevisiae
-
批准号:6920712
-
项目类别:
-
资助金额:$4.99万
-
财政年份:2003
-
负责人:WENYI FENG
-
依托单位:
Investigating of a Novel Checkpoint in S. Cerevisiae
-
批准号:6691504
-
项目类别:
-
资助金额:$4.16万
-
财政年份:2003
-
负责人:WENYI FENG
-
依托单位:
Investigating of a Novel Checkpoint in S. Cerevisiae
-
批准号:6778266
-
项目类别:
-
资助金额:$4.73万
-
财政年份:2003
-
负责人:WENYI FENG
-
依托单位:
海外基金