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The INO80 chromatin remodeling compl...
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Jiang, Yingjun.
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The INO80 chromatin remodeling complex is involved in the nucleotide excision repair pathway.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
The INO80 chromatin remodeling complex is involved in the nucleotide excision repair pathway./
作者:
Jiang, Yingjun.
面頁冊數:
127 p.
附註:
Source: Dissertation Abstracts International, Volume: 70-04, Section: B, page: 2073.
Contained By:
Dissertation Abstracts International70-04B.
標題:
Biology, Molecular. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3353991
ISBN:
9781109110289
The INO80 chromatin remodeling complex is involved in the nucleotide excision repair pathway.
Jiang, Yingjun.
The INO80 chromatin remodeling complex is involved in the nucleotide excision repair pathway.
- 127 p.
Source: Dissertation Abstracts International, Volume: 70-04, Section: B, page: 2073.
Thesis (Ph.D.)--The University of Texas Graduate School of Biomedical Sciences at Houston, 2009.
The genomic DNA of eukaryotic cells is well organized into chromatin structures. However, these repressed structures present barriers that block the access of regulatory factors to the genome during various nuclear events. To overcome the obstacle, two major cellular processes, post-modification of histone tails and ATP-dependent chromatin remodeling, are involved in reconfiguring chromatin structure and creating accessible DNA. Despite the current research progress, much remains to be explored concerning the relationship between chromatin remodeling and DNA repair. Recently, one member of the ATP-dependent chromatin remodeling complexes, INO80, has been found to play a crucial role in DNA damage repair. However, the functions of this complex in higher eukaryotes have yet to be determined. The goal of my study is to generate a human somatic INO80 conditional knockout model and investigate the functions of Ino80 in damage repair.
ISBN: 9781109110289Subjects--Topical Terms:
1017719
Biology, Molecular.
The INO80 chromatin remodeling complex is involved in the nucleotide excision repair pathway.
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The genomic DNA of eukaryotic cells is well organized into chromatin structures. However, these repressed structures present barriers that block the access of regulatory factors to the genome during various nuclear events. To overcome the obstacle, two major cellular processes, post-modification of histone tails and ATP-dependent chromatin remodeling, are involved in reconfiguring chromatin structure and creating accessible DNA. Despite the current research progress, much remains to be explored concerning the relationship between chromatin remodeling and DNA repair. Recently, one member of the ATP-dependent chromatin remodeling complexes, INO80, has been found to play a crucial role in DNA damage repair. However, the functions of this complex in higher eukaryotes have yet to be determined. The goal of my study is to generate a human somatic INO80 conditional knockout model and investigate the functions of Ino80 in damage repair.
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By homologous targeting of the INO80 locus in human HCT116 colon epithelial cells, I established a human somatic INO80 conditional knockout model. I have demonstrated that the conditional INO80 cells exhibited a sufficiently viable period when the INO80 protein is removed. Moreover, I found that loss of INO80 resulted in deficient UV lesion repair in response to UV while the protein levels of the NER factors such as XPC, XPA, XPD were not affected. And in vitro repair synthesis assay showed that the NER incision and repair synthesis activities were intact in the absence of INO80. Examination on the damage recognition factor XPC showed its recruitment to damage sites was impaired in the INO80 mutant cells. Loss of INO80 also led to reduced enrichment of XPA at the site of UV lesions. Despite the reduced recruitment of XPC and XPA observed in INO80 mutants, no direct interaction was detected. Meanwhile, direct interaction between INO80 and DDB1, the initial UV lesion detector, was detected by coimmunoprecipitation. UV-induced chromosome relaxation was reduced in cells devoid of INO80. These results demonstrate the INO80 complex may participates in the NER by interacting with DDB1 and having a critical role of in creating DNA accessibility for the nucleotide excision pathway.
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