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The ubiquitin ligase RAD18 is implic...

Watson, Nicholas Bryce.

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The ubiquitin ligase RAD18 is implicated in mutagenic translesion synthesis of DNA damage in human cells.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The ubiquitin ligase RAD18 is implicated in mutagenic translesion synthesis of DNA damage in human cells./
Author:	Watson, Nicholas Bryce.
Description:	68 p.
Notes:	Source: Masters Abstracts International, Volume: 44-01, page: 0326.
Contained By:	Masters Abstracts International44-01.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=1427277
ISBN:	9780542177491

The ubiquitin ligase RAD18 is implicated in mutagenic translesion synthesis of DNA damage in human cells.
Watson, Nicholas Bryce.

The ubiquitin ligase RAD18 is implicated in mutagenic translesion synthesis of DNA damage in human cells. - 68 p.

Source: Masters Abstracts International, Volume: 44-01, page: 0326.

Thesis (M.S.)--University of Louisville, 2005.

We are examining the molecular mechanisms of mutation induction by carcinogens, in order to reduce the incidence of cancer associated with such agents. In the yeast Saccharomyces cerevisiae, the ubiquitin ligase rad18 has been shown to be required for the successful replication of DNA past stalled replication forks after UV exposure. This protein has been extensively studied in yeast, but recently the human homolog has been discovered. Acting in conjunction with the ubiquitin-conjugating enzyme rad6, rad18 binds to sites of single-stranded DNA at sites of DNA damage by an unknown signaling mechanism. This complex acts to monoubiquitinate proliferating cell nuclear antigen (PCNA) at lysine residue 164 (K164). We hypothesize that RAD18 in humans (hRAD18) initiates the signal that recruits mutagenic translesion polymerases to the sites of stalled replication forks. To examine the rote of hRAD18, we established cell lines that have reduced levels of hRAD18 by virtue of the stable expression of ribozymes or antisense to the transcript. We found that an 85% reduction in the level of protein reduced the frequency of mutations in the HPRT gene by UV254nm or benzo[a]pyrenediolepoxide (BPDE) virtually to background levels. Using immunohistochemistry, we determined that DNA damage induced by UV or BPDE causes hRAD18 to accumulate in the nucleus in a focal pattern, although protein levels of hRAD18 remain constant as indicated by Western analysis. These foci co-localize with PCNA, the clamp protein present in DNA replication forks only when damaged in S phase of the cell cycle. These experimental data support the hypothesis that RAD18 is involved in the signaling of mutagenic translesion polymerases.

ISBN: 9780542177491Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

The ubiquitin ligase RAD18 is implicated in mutagenic translesion synthesis of DNA damage in human cells.
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100 1 $a Watson, Nicholas Bryce. $3 1916340
245 1 4 $a The ubiquitin ligase RAD18 is implicated in mutagenic translesion synthesis of DNA damage in human cells.
300 $a 68 p.
500 $a Source: Masters Abstracts International, Volume: 44-01, page: 0326.
500 $a Adviser: W. Glen McGregor.
502 $a Thesis (M.S.)--University of Louisville, 2005.
520 $a We are examining the molecular mechanisms of mutation induction by carcinogens, in order to reduce the incidence of cancer associated with such agents. In the yeast Saccharomyces cerevisiae, the ubiquitin ligase rad18 has been shown to be required for the successful replication of DNA past stalled replication forks after UV exposure. This protein has been extensively studied in yeast, but recently the human homolog has been discovered. Acting in conjunction with the ubiquitin-conjugating enzyme rad6, rad18 binds to sites of single-stranded DNA at sites of DNA damage by an unknown signaling mechanism. This complex acts to monoubiquitinate proliferating cell nuclear antigen (PCNA) at lysine residue 164 (K164). We hypothesize that RAD18 in humans (hRAD18) initiates the signal that recruits mutagenic translesion polymerases to the sites of stalled replication forks. To examine the rote of hRAD18, we established cell lines that have reduced levels of hRAD18 by virtue of the stable expression of ribozymes or antisense to the transcript. We found that an 85% reduction in the level of protein reduced the frequency of mutations in the HPRT gene by UV254nm or benzo[a]pyrenediolepoxide (BPDE) virtually to background levels. Using immunohistochemistry, we determined that DNA damage induced by UV or BPDE causes hRAD18 to accumulate in the nucleus in a focal pattern, although protein levels of hRAD18 remain constant as indicated by Western analysis. These foci co-localize with PCNA, the clamp protein present in DNA replication forks only when damaged in S phase of the cell cycle. These experimental data support the hypothesis that RAD18 is involved in the signaling of mutagenic translesion polymerases.
590 $a School code: 0110.
650 4 $a Health Sciences, Pharmacology. $3 1017717
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Biology, Cell. $3 1017686
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690 $a 0369
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710 2 0 $a University of Louisville. $3 1017614
773 0 $t Masters Abstracts International $g 44-01.
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790 $a 0110
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792 $a 2005
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=1427277