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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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2010
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| Online Access: | http://hdl.handle.net/10356/42387 |
| _version_ | 1811681135665610752 |
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| author | Ong, Michelle Shuling. |
| author2 | Curtis Alexander Davey |
| author_facet | Curtis Alexander Davey Ong, Michelle Shuling. |
| author_sort | Ong, Michelle Shuling. |
| collection | NTU |
| 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. |
| first_indexed | 2024-10-01T03:36:08Z |
| format | Thesis |
| id | ntu-10356/42387 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:36:08Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | ntu-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 |
| spellingShingle | DRNTU::Science::Biological sciences::Biochemistry Ong, Michelle Shuling. Investigation of anticancer agent and high mobility group N protein binding to nucleosomes. |
| title | 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_short | 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 |
| topic | DRNTU::Science::Biological sciences::Biochemistry |
| url | http://hdl.handle.net/10356/42387 |
| work_keys_str_mv | AT ongmichelleshuling investigationofanticanceragentandhighmobilitygroupnproteinbindingtonucleosomes |