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Nuclear Body Formation: Hierarchical...
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Salzler, Harmony R.
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Nuclear Body Formation: Hierarchical Requirements and Functional Importance.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Nuclear Body Formation: Hierarchical Requirements and Functional Importance./
作者:
Salzler, Harmony R.
面頁冊數:
180 p.
附註:
Source: Dissertation Abstracts International, Volume: 73-07(E), Section: B.
Contained By:
Dissertation Abstracts International73-07B(E).
標題:
Biology, Molecular. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3498573
ISBN:
9781267216229
Nuclear Body Formation: Hierarchical Requirements and Functional Importance.
Salzler, Harmony R.
Nuclear Body Formation: Hierarchical Requirements and Functional Importance.
- 180 p.
Source: Dissertation Abstracts International, Volume: 73-07(E), Section: B.
Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2011.
Compartmentalization is a ubiquitous feature of nuclei and comprises another level of organization beyond DNA sequence and epigenetics. Nuclear bodies are one type of compartment, participating in storage, protein complex assembly, transcription, and RNA processing. Knowledge of nuclear body structure and function is necessary for complete understanding of these processes.
ISBN: 9781267216229Subjects--Topical Terms:
1017719
Biology, Molecular.
Nuclear Body Formation: Hierarchical Requirements and Functional Importance.
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Source: Dissertation Abstracts International, Volume: 73-07(E), Section: B.
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Adviser: Robert J. Duronio.
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Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2011.
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Compartmentalization is a ubiquitous feature of nuclei and comprises another level of organization beyond DNA sequence and epigenetics. Nuclear bodies are one type of compartment, participating in storage, protein complex assembly, transcription, and RNA processing. Knowledge of nuclear body structure and function is necessary for complete understanding of these processes.
520
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Nuclear bodies consist of concentrated components in dynamic exchange with the surrounding nucleus. Evidence suggests that nuclear body formation occurs through a combination of kinetics and molecular interactions termed "self-organization". Whether self-organization is primarily stochastic or ordered remains unknown. Likewise, much is unknown about the assembly details of particular nuclear bodies, as well as their functional relationships with associated processes.
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In this thesis, I investigate the organizational requirements and consequences of one specific nuclear body, the Drosophila histone locus body (HLB). The HLB associates with the histone gene cluster, participating in the transcription and processing of histone mRNAs. Genetic evidence demonstrates that assembly of some HLB components (Mute, Lsm11) is predicated on other components (Mxc, FLASH), consistent with a model of hierarchical self-organization. My work shows that chromatin proteins H2aV, MBD-R2, and MCRS1, are required to assemble Lsm11, but not Mute, Mxc, or FLASH, constituting another hierarchical assembly step. Previously, nothing was known about the DNA sequence requirements at the histone locus enabling HLB assembly. I show that clustering of histone genes is unnecessary for HLB formation by showing that HLBs form on a single histone repeat at an ectopic genomic location. By introducing a series of ectopic histone DNA segments, I conclude that the H3-H4 transcription unit has unique HLB assembly capability, driven by the H3-H4 promoter region. This is enhanced non-specifically by additional histone sequences. Furthermore, quantitative RT-PCR correlates HLB assembly and transcript expression, and suggests that the H3-H4 unit enhances expression of neighboring histone genes. Finally, I show that mutation of Slbp and U7, (histone mRNA processing factors) causes genomic instability, including loss of heterozygosity, double strand breaks, tetraploidy, and changes in chromatin structure, with Slbp mutants also exhibiting proliferation defects. These results provide evidence for the importance of histone mRNA processing to genomic stability.
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