Eintrag weiter verarbeiten
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant.
Gespeichert in:
Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
---|---|
Personen und Körperschaften: | , , , |
In: | Proceedings of the National Academy of Sciences, 93, 1996, 7, S. 2941-2946 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
Proceedings of the National Academy of Sciences
|
Schlagwörter: |
author_facet |
Raha, M Wang, G Seidman, M M Glazer, P M Raha, M Wang, G Seidman, M M Glazer, P M |
---|---|
author |
Raha, M Wang, G Seidman, M M Glazer, P M |
spellingShingle |
Raha, M Wang, G Seidman, M M Glazer, P M Proceedings of the National Academy of Sciences Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. Multidisciplinary |
author_sort |
raha, m |
spelling |
Raha, M Wang, G Seidman, M M Glazer, P M 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.93.7.2941 <jats:p>Psoralen-conjugated triple-helix-forming oligonucleotides have been used to generate site-specific mutations within mammalian cells. To investigate factors influencing the efficiency of oligonucleotide-mediated gene targeting, the processing of third-strand-directed psoralen adducts was compared in normal and repair-deficient human cells. An unusually high mutation frequency and an altered mutation pattern were seen in xeroderma pigmentosum variant (XPV) cells compared with normal, xeroderma pigmentosum group A (XPA), and Fanconi anemia cells. In XPV, targeted mutations were produced in the supF reporter gene carried in a simian virus 40 vector at a frequency of 30%, 3-fold above that in normal or Fanconi anemia cells and 6-fold above that in XPA. The mutations generated by targeted psoralen crosslinks and monoadducts in the XPV cells formed a pattern distinct from that in the other three cell lines, with mutations occurring not just at the damaged site but also at adjacent base pairs. Hence, the XPV cells may have an abnormality in trans-lesion bypass synthesis during repair and/or replication, implicating a DNA polymerase or an accessory factor as a basis of the defect in XPV. These results may help to elucidate the repair deficiency in XPV, and they raise the possibility that genetic manipulation via triplex-targeted mutagenesis may be enhanced by modulation of the XPV-associated activity in normal cells.</jats:p> Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. Proceedings of the National Academy of Sciences |
doi_str_mv |
10.1073/pnas.93.7.2941 |
facet_avail |
Online Free |
format |
ElectronicArticle |
fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjkzLjcuMjk0MQ |
id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjkzLjcuMjk0MQ |
institution |
DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 |
imprint |
Proceedings of the National Academy of Sciences, 1996 |
imprint_str_mv |
Proceedings of the National Academy of Sciences, 1996 |
issn |
0027-8424 1091-6490 |
issn_str_mv |
0027-8424 1091-6490 |
language |
English |
mega_collection |
Proceedings of the National Academy of Sciences (CrossRef) |
match_str |
raha1996mutagenesisbythirdstranddirectedpsoralenadductsinrepairdeficienthumancellshighfrequencyandalteredspectruminaxerodermapigmentosumvariant |
publishDateSort |
1996 |
publisher |
Proceedings of the National Academy of Sciences |
recordtype |
ai |
record_format |
ai |
series |
Proceedings of the National Academy of Sciences |
source_id |
49 |
title |
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_unstemmed |
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_full |
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_fullStr |
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_full_unstemmed |
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_short |
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_sort |
mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
topic |
Multidisciplinary |
url |
http://dx.doi.org/10.1073/pnas.93.7.2941 |
publishDate |
1996 |
physical |
2941-2946 |
description |
<jats:p>Psoralen-conjugated triple-helix-forming oligonucleotides have been used to generate site-specific mutations within mammalian cells. To investigate factors influencing the efficiency of oligonucleotide-mediated gene targeting, the processing of third-strand-directed psoralen adducts was compared in normal and repair-deficient human cells. An unusually high mutation frequency and an altered mutation pattern were seen in xeroderma pigmentosum variant (XPV) cells compared with normal, xeroderma pigmentosum group A (XPA), and Fanconi anemia cells. In XPV, targeted mutations were produced in the supF reporter gene carried in a simian virus 40 vector at a frequency of 30%, 3-fold above that in normal or Fanconi anemia cells and 6-fold above that in XPA. The mutations generated by targeted psoralen crosslinks and monoadducts in the XPV cells formed a pattern distinct from that in the other three cell lines, with mutations occurring not just at the damaged site but also at adjacent base pairs. Hence, the XPV cells may have an abnormality in trans-lesion bypass synthesis during repair and/or replication, implicating a DNA polymerase or an accessory factor as a basis of the defect in XPV. These results may help to elucidate the repair deficiency in XPV, and they raise the possibility that genetic manipulation via triplex-targeted mutagenesis may be enhanced by modulation of the XPV-associated activity in normal cells.</jats:p> |
container_issue |
7 |
container_start_page |
2941 |
container_title |
Proceedings of the National Academy of Sciences |
container_volume |
93 |
format_de105 |
Article, E-Article |
format_de14 |
Article, E-Article |
format_de15 |
Article, E-Article |
format_de520 |
Article, E-Article |
format_de540 |
Article, E-Article |
format_dech1 |
Article, E-Article |
format_ded117 |
Article, E-Article |
format_degla1 |
E-Article |
format_del152 |
Buch |
format_del189 |
Article, E-Article |
format_dezi4 |
Article |
format_dezwi2 |
Article, E-Article |
format_finc |
Article, E-Article |
format_nrw |
Article, E-Article |
_version_ |
1792337406904500234 |
geogr_code |
not assigned |
last_indexed |
2024-03-01T15:15:50.563Z |
geogr_code_person |
not assigned |
openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Mutagenesis+by+third-strand-directed+psoralen+adducts+in+repair-deficient+human+cells%3A+high+frequency+and+altered+spectrum+in+a+xeroderma+pigmentosum+variant.&rft.date=1996-04-02&genre=article&issn=1091-6490&volume=93&issue=7&spage=2941&epage=2946&pages=2941-2946&jtitle=Proceedings+of+the+National+Academy+of+Sciences&atitle=Mutagenesis+by+third-strand-directed+psoralen+adducts+in+repair-deficient+human+cells%3A+high+frequency+and+altered+spectrum+in+a+xeroderma+pigmentosum+variant.&aulast=Glazer&aufirst=P+M&rft_id=info%3Adoi%2F10.1073%2Fpnas.93.7.2941&rft.language%5B0%5D=eng |
SOLR | |
_version_ | 1792337406904500234 |
author | Raha, M, Wang, G, Seidman, M M, Glazer, P M |
author_facet | Raha, M, Wang, G, Seidman, M M, Glazer, P M, Raha, M, Wang, G, Seidman, M M, Glazer, P M |
author_sort | raha, m |
container_issue | 7 |
container_start_page | 2941 |
container_title | Proceedings of the National Academy of Sciences |
container_volume | 93 |
description | <jats:p>Psoralen-conjugated triple-helix-forming oligonucleotides have been used to generate site-specific mutations within mammalian cells. To investigate factors influencing the efficiency of oligonucleotide-mediated gene targeting, the processing of third-strand-directed psoralen adducts was compared in normal and repair-deficient human cells. An unusually high mutation frequency and an altered mutation pattern were seen in xeroderma pigmentosum variant (XPV) cells compared with normal, xeroderma pigmentosum group A (XPA), and Fanconi anemia cells. In XPV, targeted mutations were produced in the supF reporter gene carried in a simian virus 40 vector at a frequency of 30%, 3-fold above that in normal or Fanconi anemia cells and 6-fold above that in XPA. The mutations generated by targeted psoralen crosslinks and monoadducts in the XPV cells formed a pattern distinct from that in the other three cell lines, with mutations occurring not just at the damaged site but also at adjacent base pairs. Hence, the XPV cells may have an abnormality in trans-lesion bypass synthesis during repair and/or replication, implicating a DNA polymerase or an accessory factor as a basis of the defect in XPV. These results may help to elucidate the repair deficiency in XPV, and they raise the possibility that genetic manipulation via triplex-targeted mutagenesis may be enhanced by modulation of the XPV-associated activity in normal cells.</jats:p> |
doi_str_mv | 10.1073/pnas.93.7.2941 |
facet_avail | Online, Free |
format | ElectronicArticle |
format_de105 | Article, E-Article |
format_de14 | Article, E-Article |
format_de15 | Article, E-Article |
format_de520 | Article, E-Article |
format_de540 | Article, E-Article |
format_dech1 | Article, E-Article |
format_ded117 | Article, E-Article |
format_degla1 | E-Article |
format_del152 | Buch |
format_del189 | Article, E-Article |
format_dezi4 | Article |
format_dezwi2 | Article, E-Article |
format_finc | Article, E-Article |
format_nrw | Article, E-Article |
geogr_code | not assigned |
geogr_code_person | not assigned |
id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA3My9wbmFzLjkzLjcuMjk0MQ |
imprint | Proceedings of the National Academy of Sciences, 1996 |
imprint_str_mv | Proceedings of the National Academy of Sciences, 1996 |
institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
issn | 0027-8424, 1091-6490 |
issn_str_mv | 0027-8424, 1091-6490 |
language | English |
last_indexed | 2024-03-01T15:15:50.563Z |
match_str | raha1996mutagenesisbythirdstranddirectedpsoralenadductsinrepairdeficienthumancellshighfrequencyandalteredspectruminaxerodermapigmentosumvariant |
mega_collection | Proceedings of the National Academy of Sciences (CrossRef) |
physical | 2941-2946 |
publishDate | 1996 |
publishDateSort | 1996 |
publisher | Proceedings of the National Academy of Sciences |
record_format | ai |
recordtype | ai |
series | Proceedings of the National Academy of Sciences |
source_id | 49 |
spelling | Raha, M Wang, G Seidman, M M Glazer, P M 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.93.7.2941 <jats:p>Psoralen-conjugated triple-helix-forming oligonucleotides have been used to generate site-specific mutations within mammalian cells. To investigate factors influencing the efficiency of oligonucleotide-mediated gene targeting, the processing of third-strand-directed psoralen adducts was compared in normal and repair-deficient human cells. An unusually high mutation frequency and an altered mutation pattern were seen in xeroderma pigmentosum variant (XPV) cells compared with normal, xeroderma pigmentosum group A (XPA), and Fanconi anemia cells. In XPV, targeted mutations were produced in the supF reporter gene carried in a simian virus 40 vector at a frequency of 30%, 3-fold above that in normal or Fanconi anemia cells and 6-fold above that in XPA. The mutations generated by targeted psoralen crosslinks and monoadducts in the XPV cells formed a pattern distinct from that in the other three cell lines, with mutations occurring not just at the damaged site but also at adjacent base pairs. Hence, the XPV cells may have an abnormality in trans-lesion bypass synthesis during repair and/or replication, implicating a DNA polymerase or an accessory factor as a basis of the defect in XPV. These results may help to elucidate the repair deficiency in XPV, and they raise the possibility that genetic manipulation via triplex-targeted mutagenesis may be enhanced by modulation of the XPV-associated activity in normal cells.</jats:p> Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. Proceedings of the National Academy of Sciences |
spellingShingle | Raha, M, Wang, G, Seidman, M M, Glazer, P M, Proceedings of the National Academy of Sciences, Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant., Multidisciplinary |
title | Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_full | Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_fullStr | Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_full_unstemmed | Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_short | Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_sort | mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
title_unstemmed | Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. |
topic | Multidisciplinary |
url | http://dx.doi.org/10.1073/pnas.93.7.2941 |