Assembly and epigenetic inheritance of the human centromere
Assembly and epigenetic inheritance of the human centromere
批准号:
10463586
负责人:
Daniel Richard Foltz
金额:
$33.18万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-08-01 至 2023-07-31
关键词:
AddressAffectAneuploidyBindingBiologicalBiologyCRISPR/Cas technologyCell CycleCell divisionCentromereCharacteristicsChromatinChromatin ModelingChromosome ArmChromosome SegregationChromosomesComplexDAXX geneDNADNA SequenceDNA biosynthesisDNA replication forkDataDepositionEnsureEpigenetic ProcessFundingGenomeGenomic InstabilityGenomicsGrantHistone H3HistonesHumanIndividualKinetochoresLeadMCM2 geneMaintenanceMalignant NeoplasmsMediatingMethodsMitosisMitoticMitotic spindleMolecularMolecular ChaperonesNatureNucleosomesOncogenesPhasePost-Translational Protein ProcessingProcessProteinsRoleS phaseSatellite DNASignal TransductionSiteSpecific qualifier valueVariantWorkcentromere protein Achromosome missegregationchromosome movementexperimental studyinhibitornovelrecruitreplication stress
中文摘要
染色体错误分离和非整倍体是肿瘤的常见特征。
着丝粒是确定动粒形成位点的染色体基因座,
确保在有丝分裂期间染色体的可靠分离。着丝粒同一性是
表观遗传学上通过CENP-A核小体的掺入来指定,独立于
DNA序列由于着丝粒的染色质性质,
控制CENP-A核小体组装和核小体稳定性是必不可少的,
着丝粒特化的维持。必须将新的CENP-A添加到着丝粒上
在每个细胞周期中以一致和忠实的方式维持着丝粒
染色质和着丝粒的同一性。新的CENP-A核小体被添加到
着丝粒在G1期间被CENP-A特异性伴侣HJURP,其被招募以
由Mis 18复合体组成。虽然与经典组蛋白H3不同,新CENP-A
在DNA复制过程中不沉积;然而,CENP-A核小体保留在
DNA复制过程中的着丝粒,以确保着丝粒的透射率
基因座CENP-A核小体稳定保留的机制,
染色质在DNA复制过程中被分解的问题将在本申请中解决。
着丝粒位于大多数个体的α-卫星DNA重复序列内;
然而,已经鉴定出几种新着丝粒,
在非着丝粒位点重新定位和发挥作用。该应用程序将解决以下问题:
非着丝粒位点获得着丝粒身份,以了解
染色质和基因组对着丝粒功能的贡献。
英文摘要
Chromosome missegregation and aneuploidy are commons characteristics of cancer.
Centromeres are chromosomal loci that define the site of kinetochore formation and
ensure faithful chromosome segregation during mitosis. Centromeric identity is
epigenetically specified by the incorporation of CENP-A nucleosomes, independent of
DNA sequence. Because of the chromatin nature of the centromere, the processes that
govern CENP-A nucleosome assembly and nucleosome stability are essential to the
maintenance of centromere specification. New CENP-A must be added to the centromere
in a consistent and faithful manner during each cell cycle to maintain centromeric
chromatin and centromere identity. New CENP-A nucleosomes are added to the
centromere during G1 by the CENP-A specific chaperone HJURP, that is recruited to
centromere by the Mis18 complex. Although unlike canonical histone H3, new CENP-A
is not deposited during DNA replication; however, CENP-A nucleosomes are retained at
the centromere during DNA replication to ensure the transmittance of the centromeric
locus. The mechanism by which CENP-A nucleosomes are stably retained when
chromatin is disassembled during DNA replication will be addressed in this application.
Centromeres are located within the alpha-satellite DNA repeats in most individuals;
however, several neocentromeres have been identified where centromere proteins
relocate and function at non-centromeric sites. This application will address the ability of
non-centromeric sites to acquire centromeric identity in order to understand the
chromatin and genomic contributions to centromere function.
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DOI:
10.1091/mbc.e22-06-0237
发表时间:
2023-04-01
期刊:
MOLECULAR BIOLOGY OF THE CELL
影响因子:
3.3
作者:
[Rodrigues, Aaron, MacQuarrie, Kyle L., Freeman, Emma, Lin, Alicia, Willis, Alexander B., Xu, Zhaofa, Alvarez, Angel A., Ma, Yongchao, White, Bethany E. Perez, Foltz, Daniel R., Huang, Sui]
通讯作者:
Huang, Sui
DOI:
10.1007/s00412-018-0665-x
发表时间:
2018-09
期刊:
Chromosoma
影响因子:
1.6
作者:
[Srivastava S, Foltz DR]
通讯作者:
Foltz DR
The histone H3/H4 chaperone CHAF1B prevents the mislocalization of CENP-A for chromosomal stability.
DOI:
10.1242/jcs.260944
发表时间:
2023-05-15
期刊:
Journal of cell science
影响因子:
4
作者:
[]
通讯作者:
Mislocalization of centromeric histone H3 variant CENP-A contributes to chromosomal instability (CIN) in human cells.
着丝粒组蛋白 H3 变体 CENP-A 的错误定位会导致人类细胞染色体不稳定 (CIN)。
DOI:
10.18632/oncotarget.18108
发表时间:
2017-07-18
期刊:
Oncotarget
影响因子:
--
作者:
[Shrestha RL, Ahn GS, Staples MI, Sathyan KM, Karpova TS, Foltz DR, Basrai MA]
通讯作者:
Basrai MA
DOI:
10.1083/jcb.202007195
发表时间:
2021-04-05
期刊:
The Journal of cell biology
影响因子:
--
作者:
[Shrestha RL, Rossi A, Wangsa D, Hogan AK, Zaldana KS, Suva E, Chung YJ, Sanders CL, Difilippantonio S, Karpova TS, Karim B, Foltz DR, Fachinetti D, Aplan PD, Ried T, Basrai MA]
通讯作者:
Basrai MA
共 11 条
Histone chaperone networks for new and evicted histones
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批准号:10649735
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项目类别:
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资助金额:$33.02万
-
财政年份:2021
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负责人:Daniel Richard Foltz
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依托单位:
Histone chaperone networks for new and evicted histones
-
批准号:10290042
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项目类别:
-
资助金额:$33.02万
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财政年份:2021
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负责人:Daniel Richard Foltz
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依托单位:
Histone chaperone networks for new and evicted histones
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批准号:10458694
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项目类别:
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资助金额:$33.06万
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财政年份:2021
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依托单位:
The role of the nucleolus in human genome organization in normal and disease states
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批准号:10267205
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项目类别:
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资助金额:$63.1万
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财政年份:2020
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负责人:Daniel Richard Foltz
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依托单位:
The role of the nucleolus in human genome organization in normal and disease states
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批准号:10117559
-
项目类别:
-
资助金额:$64.3万
-
财政年份:2020
-
负责人:Daniel Richard Foltz
-
依托单位:
The role of the nucleolus in human genome organization in normal and disease states
-
批准号:10468754
-
项目类别:
-
资助金额:$63.1万
-
财政年份:2020
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负责人:Daniel Richard Foltz
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依托单位:
The role of the nucleolus in human genome organization in normal and disease states
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批准号:10705594
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项目类别:
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资助金额:$54.48万
-
财政年份:2020
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负责人:Daniel Richard Foltz
-
依托单位:
Assembly and epigenetic inheritance of the human centromere
-
批准号:9119625
-
项目类别:
-
资助金额:$29.0万
-
财政年份:2015
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负责人:Daniel Richard Foltz
-
依托单位:
Assembly and epigenetic inheritance of the human centromere
-
批准号:8765120
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项目类别:
-
资助金额:$29.96万
-
财政年份:2014
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负责人:Daniel Richard Foltz
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依托单位:
UBR7 is a novel chromatin directed E3 ubiquitin ligase
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批准号:8770744
-
项目类别:
-
资助金额:$19.45万
-
财政年份:2014
-
负责人:Daniel Richard Foltz
-
依托单位:
Assembly and epigenetic inheritance of the human centromere
-
批准号:10224745
-
项目类别:
-
资助金额:$33.18万
-
财政年份:2014
-
负责人:Daniel Richard Foltz
-
依托单位:
The role of CENP-A in mammalian centromere specification
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批准号:6844876
-
项目类别:
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资助金额:$4.99万
-
财政年份:2003
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负责人:Daniel Richard Foltz
-
依托单位:
The role of CENP-A in mammalian centromere specification
-
批准号:6710665
-
项目类别:
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资助金额:$4.73万
-
财政年份:2003
-
负责人:Daniel Richard Foltz
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依托单位:
The role of CENP-A in mammalian centromere specification
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批准号:6584108
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项目类别:
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资助金额:$4.16万
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财政年份:2003
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负责人:Daniel Richard Foltz
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依托单位:
海外基金