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Functional analysis of murine DNA to...
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Kwan, Kelvin Y.
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Functional analysis of murine DNA topoisomerase IIIbeta.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Functional analysis of murine DNA topoisomerase IIIbeta./
作者:
Kwan, Kelvin Y.
面頁冊數:
155 p.
附註:
Adviser: James C. Wang.
Contained By:
Dissertation Abstracts International63-04B.
標題:
Biology, Genetics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3051210
ISBN:
0493657428
Functional analysis of murine DNA topoisomerase IIIbeta.
Kwan, Kelvin Y.
Functional analysis of murine DNA topoisomerase IIIbeta.
- 155 p.
Adviser: James C. Wang.
Thesis (Ph.D.)--Harvard University, 2002.
From all the sequenced genomes, it is evident that each class of DNA topoisomerases is well conserved throughout. DNA topoisomerases are enzymes that catalyze the passage of DNA strands through one another. Inside the cell, DNA topoisomerases mainly deal with topological constraints that arise from macromolecular processes such as replication, transcription, and recombination. To understand the <italic>in vivo</italic> function of mammalian DNA topoisomerase IIIβ, a type IA DNA topoisomerase, targeted disruption of the <italic> TOP3</italic>β gene in mice was carried out. The initial observation of a shortened mean lifespan in <italic>top3</italic>β<super>−/− </super> mice led to a more detailed characterization of these mice. Because of the physical and functional interactions between the type IA subfamily of DNA topoisomerases and the RecQ helicases, our investigation was directed towards manifestations in <italic>top3</italic>β<super>−/− </super> mice that were similar to those observed in human RecQ helicase syndromes. From immunological studies, an increased level of autoantibodies caused by spontaneous activation of T cells was observed in the <italic>top3</italic>β<super> −/−</super> mice. In the course of mating and maintaining the <italic> top3</italic>β<super>−/−</super> animals, a decrease in fertility was observed. The lack of <italic>TOP3</italic>β affected the fertility of male much more than female mice. Immunocytology suggested that DNA topoisomerase IIIβ may function at the XY bivalent in male mice to resolve DNA repair or recombination intermediates. The involvement of DNA topoisomerase IIIβ in resolving repair or recombination intermediates is further supported by the results that <italic>top3</italic>β<super>−/− </super> embryonic stem cells are more sensitive to ionizing radiation. Together these results suggest a role for DNA topoisomerase IIIβ in the resolution of DNA intermediates that arise after DNA damage, and the subsequent lack of DNA topoisomerase IIIβ in mice leads to manifestations similar to some RecQ helicase syndromes.
ISBN: 0493657428Subjects--Topical Terms:
1017730
Biology, Genetics.
Functional analysis of murine DNA topoisomerase IIIbeta.
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From all the sequenced genomes, it is evident that each class of DNA topoisomerases is well conserved throughout. DNA topoisomerases are enzymes that catalyze the passage of DNA strands through one another. Inside the cell, DNA topoisomerases mainly deal with topological constraints that arise from macromolecular processes such as replication, transcription, and recombination. To understand the <italic>in vivo</italic> function of mammalian DNA topoisomerase IIIβ, a type IA DNA topoisomerase, targeted disruption of the <italic> TOP3</italic>β gene in mice was carried out. The initial observation of a shortened mean lifespan in <italic>top3</italic>β<super>−/− </super> mice led to a more detailed characterization of these mice. Because of the physical and functional interactions between the type IA subfamily of DNA topoisomerases and the RecQ helicases, our investigation was directed towards manifestations in <italic>top3</italic>β<super>−/− </super> mice that were similar to those observed in human RecQ helicase syndromes. From immunological studies, an increased level of autoantibodies caused by spontaneous activation of T cells was observed in the <italic>top3</italic>β<super> −/−</super> mice. In the course of mating and maintaining the <italic> top3</italic>β<super>−/−</super> animals, a decrease in fertility was observed. The lack of <italic>TOP3</italic>β affected the fertility of male much more than female mice. Immunocytology suggested that DNA topoisomerase IIIβ may function at the XY bivalent in male mice to resolve DNA repair or recombination intermediates. The involvement of DNA topoisomerase IIIβ in resolving repair or recombination intermediates is further supported by the results that <italic>top3</italic>β<super>−/− </super> embryonic stem cells are more sensitive to ionizing radiation. Together these results suggest a role for DNA topoisomerase IIIβ in the resolution of DNA intermediates that arise after DNA damage, and the subsequent lack of DNA topoisomerase IIIβ in mice leads to manifestations similar to some RecQ helicase syndromes.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3051210
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