國立高雄大學圖資館 |

Language: English

Back

Structural and biochemical studies on human 8-oxoguanine DNA glycosylase, and transcriptional profiling of the Escherichia coli adaptive response to alkylation.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Structural and biochemical studies on human 8-oxoguanine DNA glycosylase, and transcriptional profiling of the Escherichia coli adaptive response to alkylation.
Author:	Norman, Derek Paul Geoffrey.
Description:	121 p.
Notes:	Adviser: Gregory L. Verdine.
Notes:	Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2177.
Contained By:	Dissertation Abstracts International64-05B.
Subject:	Chemistry, Biochemistry.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3091649
ISBN:	0496393588

Structural and biochemical studies on human 8-oxoguanine DNA glycosylase, and transcriptional profiling of the Escherichia coli adaptive response to alkylation.
Norman, Derek Paul Geoffrey.

Structural and biochemical studies on human 8-oxoguanine DNA glycosylase, and transcriptional profiling of the Escherichia coli adaptive response to alkylation. [electronic resource] - 121 p.

Adviser: Gregory L. Verdine.

Thesis (Ph.D.)--Harvard University, 2003.

DNA is subject to modification by various reactive compounds, including reactive oxygen species (ROS) and alkylating agents. One of the principal products of oxidative DNA damage is the mutagenic base 8-oxoguanine (oxoG), which can form a base pair with adenine during DNA replication, ultimately leading to a transversion mutation. In humans, oxoG paired with cytosine is recognized and removed by the enzyme human 8-oxoguanine glycosylase (hOgg1). hOgg1 uses an internal lysine residue (Lys 249) to displace the glycosidic bond. An aspartate residue, Asp 268, is also required for catalysis.

ISBN: 0496393588Subjects--Topical Terms:

226900
Chemistry, Biochemistry.

Structural and biochemical studies on human 8-oxoguanine DNA glycosylase, and transcriptional profiling of the Escherichia coli adaptive response to alkylation.
LDR:03426nmm _2200289 _450 001 162033
005 20051017073403.5
008 230606s2003 eng d
020 $a 0496393588
035 $a 00148534
035 $a 162033
040 $a UnM $c UnM
100 0 $a Norman, Derek Paul Geoffrey. $3 227137
245 1 0 $a Structural and biochemical studies on human 8-oxoguanine DNA glycosylase, and transcriptional profiling of the Escherichia coli adaptive response to alkylation. $h [electronic resource]
300 $a 121 p.
500 $a Adviser: Gregory L. Verdine.
500 $a Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2177.
502 $a Thesis (Ph.D.)--Harvard University, 2003.
520 # $a DNA is subject to modification by various reactive compounds, including reactive oxygen species (ROS) and alkylating agents. One of the principal products of oxidative DNA damage is the mutagenic base 8-oxoguanine (oxoG), which can form a base pair with adenine during DNA replication, ultimately leading to a transversion mutation. In humans, oxoG paired with cytosine is recognized and removed by the enzyme human 8-oxoguanine glycosylase (hOgg1). hOgg1 uses an internal lysine residue (Lys 249) to displace the glycosidic bond. An aspartate residue, Asp 268, is also required for catalysis.
520 # $a Like oxidation, alkylating agents can modify the base-pairing properties of DNA. Methylated Ada protein is the transcription factor that initiates the E. coli adaptive response to alkylation, which activates transcription of three DNA repair genes (ada, alkA , and alkB) and one gene of unknown function ( aidB). Genome-wide transcriptional profiling experiments were performed to identify previously unidentified genes that are part of the adaptive response. One highly induced gene, csgA, encodes the protein curlin, which polymerizes on the extracellular surface of the bacteria to form curli fimbriae. Further experiments showed that the csgA promoter is turned on by methylated Ada; a physical interaction was also observed in vitro using template directed interference (TDI) footprinting.
520 # $a The crystal structure of wild-type hOgg1 bound to an abasic tetrahydrofuranyl allows further insight into the catalytic mechanism of hOgg1. Studies into the role of Asp 268 showed that this helix-capping residue is crucial for the stability of the folded form of hOgg1. The crystal structure of D268N hOgg1 bound to oxoG-containing DNA indicates that Asp 268 electrostatically stabilizes the oxocarbenium intermediate that forms during base-excision, rather than acts as a general base for Lys 249.
520 # $a Three residues in hOgg1 engage in a dense array of interactions with the partner cytosine. A mutant of one of these residues (R154H) was previously identified from a cancer cell line. This mutant protein, R154H hOgg1, is less active than wild-type hOgg1 in vitro, but has lower specificity for the oxoG partner. Crystal structures of R154H hOgg1 bound to DNA containing three different estranged bases reveal a less stringent recognition pocket.
590 $a School code: 0084.
650 # 0 $a Chemistry, Biochemistry. $3 226900
710 0 # $a Harvard University. $3 212445
773 0 # $g 64-05B. $t Dissertation Abstracts International
790 $a 0084
790 1 0 $a Verdine, Gregory L., $e advisor
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://libsw.nuk.edu.tw/login?url=http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3091649 $z http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3091649