Investigation of anticancer agent and high mobility group N protein binding to nucleosomes.

By influencing nuclear factor recognition through modulation of double helix conformation and context, nucleosome structure and organization are key to understanding genomic regulation and the activity of DNA-binding medicinal agents. DNA stretching in the nucleosome, coinciding with kinking and in...

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Main Author: Ong, Michelle Shuling.
Other Authors: Curtis Alexander Davey
Format: Theses and Dissertations
Language:English
Published: 2010
Subjects:
Online Access:http://hdl.handle.net/10356/42387
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-423872023-02-28T18:34:55Z Investigation of anticancer agent and high mobility group N protein binding to nucleosomes. Ong, Michelle Shuling. Curtis Alexander Davey School of Biological Sciences DRNTU::Science::Biological sciences::Biochemistry By influencing nuclear factor recognition through modulation of double helix conformation and context, nucleosome structure and organization are key to understanding genomic regulation and the activity of DNA-binding medicinal agents. DNA stretching in the nucleosome, coinciding with kinking and increased twist in the double helix, occurs in the solution state, is ubiquitous in crystal structures of the nucleosome core particle (NCP) and appears to be commonplace in chromatin. We carried out a crystallographic study on a NCP composed of a 145 bp DNA (NCP145) at 2.65 Å resolution and found that minute alterations in DNA sequence and positioning on the histone octamer can elicit profound changes in double helix conformation. NCP145 displays two incidences of DNA stretching around the nucleosome centre, which has enabled us to characterize the basic mechanics of the phenomenon. Moreover, one site of stretching displays an extraordinary kink into the minor groove at a location that is a known hotspot for retroviral gene insertion. Such extreme DNA distortions in the nucleosome may influence other genomic processes, and we have hypothesized that they could modulate binding of DNA-associating medicinal agents. Doctor of Philosophy (SBS) 2010-11-30T03:03:20Z 2010-11-30T03:03:20Z 2010 2010 Thesis http://hdl.handle.net/10356/42387 en 181 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Biochemistry
spellingShingle DRNTU::Science::Biological sciences::Biochemistry
Ong, Michelle Shuling.
Investigation of anticancer agent and high mobility group N protein binding to nucleosomes.
description By influencing nuclear factor recognition through modulation of double helix conformation and context, nucleosome structure and organization are key to understanding genomic regulation and the activity of DNA-binding medicinal agents. DNA stretching in the nucleosome, coinciding with kinking and increased twist in the double helix, occurs in the solution state, is ubiquitous in crystal structures of the nucleosome core particle (NCP) and appears to be commonplace in chromatin. We carried out a crystallographic study on a NCP composed of a 145 bp DNA (NCP145) at 2.65 Å resolution and found that minute alterations in DNA sequence and positioning on the histone octamer can elicit profound changes in double helix conformation. NCP145 displays two incidences of DNA stretching around the nucleosome centre, which has enabled us to characterize the basic mechanics of the phenomenon. Moreover, one site of stretching displays an extraordinary kink into the minor groove at a location that is a known hotspot for retroviral gene insertion. Such extreme DNA distortions in the nucleosome may influence other genomic processes, and we have hypothesized that they could modulate binding of DNA-associating medicinal agents.
author2 Curtis Alexander Davey
author_facet Curtis Alexander Davey
Ong, Michelle Shuling.
format Theses and Dissertations
author Ong, Michelle Shuling.
author_sort Ong, Michelle Shuling.
title Investigation of anticancer agent and high mobility group N protein binding to nucleosomes.
title_short Investigation of anticancer agent and high mobility group N protein binding to nucleosomes.
title_full Investigation of anticancer agent and high mobility group N protein binding to nucleosomes.
title_fullStr Investigation of anticancer agent and high mobility group N protein binding to nucleosomes.
title_full_unstemmed Investigation of anticancer agent and high mobility group N protein binding to nucleosomes.
title_sort investigation of anticancer agent and high mobility group n protein binding to nucleosomes.
publishDate 2010
url http://hdl.handle.net/10356/42387
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