Transcription-mediated binding of peptide nucleic acid (PNA) to double-stranded DNA: Sequence-specific suicide transcription

被引:102
作者
Larsen, HJ [1 ]
Nielsen, PE [1 ]
机构
[1] UNIV COPENHAGEN, PANUM INST, CTR BIOMOLEC RECOGNIT, DEPT MED BIOCHEM & GENET, DK-2200 COPENHAGEN N, DENMARK
关键词
D O I
10.1093/nar/24.3.458
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Peptide nucleic acid (PNA) forms sequence-specific (PNA)(2)/DNA triplexes with one strand of double-stranded DNA by strand invasion. When formed with the template strand of DNA such a (PNA)(2)/DNA tripler can arrest transcription elongation in vifro and can thus act as an anti-gene agent. One of the major obstacles to applying PNA as an anti-gene agent in vivo is that PNA strand invasion occurs at a very slow rate under moderate salt conditions. In the present study we show that transcription can increase the rate of sequence-specific PNA binding dramatically. Such transcription-mediated PNA binding occurs three times as efficiently when the PNA target is situated on the non-template strand as compared with the template strand. Since transcription can mediate template strand-associated (PNA)(2)/DNA complexes which arrest further elongation, the action of RNA polymerase results in repression of its own activity, i.e. suicide transcription. These findings are highly relevant for the possible future use of PNA as an anti-gene agent.
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收藏
页码:458 / 463
页数:6
相关论文
共 22 条
  • [1] DNA UNWINDING UPON STRAND-DISPLACEMENT BINDING OF A THYMINE-SUBSTITUTED POLYAMIDE TO DOUBLE-STRANDED DNA
    CHERNY, DY
    BELOTSERKOVSKII, BP
    FRANKKAMENETSKII, MD
    EGHOLM, M
    BUCHARDT, O
    BERG, RH
    NIELSEN, PE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (05) : 1667 - 1670
  • [2] DESIGNING DNA-BINDING PROTEINS ON THE SURFACE OF FILAMENTOUS PHAGE
    CHOO, Y
    KLUG, A
    [J]. CURRENT OPINION IN BIOTECHNOLOGY, 1995, 6 (04) : 431 - 436
  • [3] CHRISTENSEN L, 1995, J PEPT SCI, V1, P175, DOI DOI 10.1002/PSC.310010304
  • [4] SEQUENCE SELECTIVE DOUBLE-STRAND DNA CLEAVAGE BY PEPTIDE NUCLEIC-ACID (PNA) TARGETING USING NUCLEASE S1
    DEMIDOV, V
    FRANKKAMENETSKII, MD
    EGHOLM, M
    BUCHARDT, O
    NIELSEN, PE
    [J]. NUCLEIC ACIDS RESEARCH, 1993, 21 (09) : 2103 - 2107
  • [5] KINETICS AND MECHANISM OF POLYAMIDE (PEPTIDE) NUCLEIC-ACID BINDING TO DUPLEX DNA
    DEMIDOV, VV
    YAVNILOVICH, MV
    BELOTSERKOVSKII, BP
    FRANKKAMENETSKII, MD
    NIELSEN, PE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (07) : 2637 - 2641
  • [6] ELECTRON-MICROSCOPY MAPPING OF OLIGOPURINE TRACTS IN DUPLEX DNA BY PEPTIDE NUCLEIC-ACID TARGETING
    DEMIDOV, VV
    CHERNY, DI
    KURAKIN, AV
    YAVNILOVICH, MV
    MALKOV, VA
    FRANKKAMENETSKII, MD
    SONNICHSEN, SH
    NIELSEN, PE
    [J]. NUCLEIC ACIDS RESEARCH, 1994, 22 (24) : 5218 - 5222
  • [7] EFFICIENT PH-INDEPENDENT SEQUENCE-SPECIFIC DNA-BINDING BY PSEUDOISOCYTOSINE-CONTAINING BIS-PNA
    EGHOLM, M
    CHRISTENSEN, L
    DUEHOLM, KL
    BUCHARDT, O
    COULL, J
    NIELSEN, PE
    [J]. NUCLEIC ACIDS RESEARCH, 1995, 23 (02) : 217 - 222
  • [8] PEPTIDE NUCLEIC-ACIDS (PNA) - OLIGONUCLEOTIDE ANALOGS WITH AN ACHIRAL PEPTIDE BACKBONE
    EGHOLM, M
    BUCHARDT, O
    NIELSEN, PE
    BERG, RH
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (05) : 1895 - 1897
  • [9] RECOGNITION OF GUANINE AND ADENINE IN DNA BY CYTOSINE AND THYMINE CONTAINING PEPTIDE NUCLEIC-ACIDS (PNA)
    EGHOLM, M
    NIELSEN, PE
    BUCHARDT, O
    BERG, RH
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (24) : 9677 - 9678
  • [10] ANTISENSE AND ANTIGENE PROPERTIES OF PEPTIDE NUCLEIC-ACIDS
    HANVEY, JC
    PEFFER, NJ
    BISI, JE
    THOMSON, SA
    CADILLA, R
    JOSEY, JA
    RICCA, DJ
    HASSMAN, CF
    BONHAM, MA
    AU, KG
    CARTER, SG
    BRUCKENSTEIN, DA
    BOYD, AL
    NOBLE, SA
    BABISS, LE
    [J]. SCIENCE, 1992, 258 (5087) : 1481 - 1485