A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes

Lee, Jeremy S.; Burkholder, Gary D.; Latimer, L.; Haug, Brenda L.; Braun, Ralph

doi:10.1093/nar/15.3.1047

Cited by 112 publications

(58 citation statements)

References 32 publications

(32 reference statements)

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“…In contrast, a perfect internal symmetry of the half-sites would signi®cantly decrease the structural¯exibility of the target DNA, rendering conformational shifting energetically di cult, if not impossible. Formation of non-B-DNA in vivo has been documented (Lee et al, 1987;Sen and Gilbert, 1988;Wittig et al, 1989Wittig et al, , 1992Ward et al, 1991;Michelotti et al, 1996), and topologically constrained chromosomal DNA undergoes conformational changes that are regulated and coordinated with cellular processes (reviewed in: DroÈ ge, 1994;van Holde and Zlatanova, 1994;Leach, 1994). Structural transitions may be supported by other proteins that could stabilize or even promote the extrusion of the alternative conformations.…”

Section: Discussionmentioning

confidence: 99%

DNA-conformation is an important determinant of sequence-specific DNA binding by tumor suppressor p53

1997

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Sequence-speci®c transactivation of target genes is one of the most important molecular properties of the tumor suppressor p53. Binding of p53 to its target DNAs is tightly regulated, with modi®cations in the carboxyterminal regulatory domain of the p53 protein playing an important role. In this study we examined the possible in¯uence of DNA structure on sequence-speci®c DNA binding by p53, by analysing its binding to p53 consensus elements adopting di erent conformations. We found that p53 has the ability to bind to consensus elements which are present in a double-helical form, as well as to consensus elements which are located within alternative non-B-DNA structures. The ability of a consensus element to adopt either one of these conformations is dependent on its sequence symmetry, and is strongly in¯uenced by its sequence environment. Our data suggest a model according to which the conformational status of the target DNA is an important determinant for sequence-speci®c DNA binding by p53. Modi®cations in the carboxy-terminal regulatory region of p53 possibly determine the preference of p53 for a given DNA conformation.

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Section: Discussionmentioning

confidence: 99%

DNA-conformation is an important determinant of sequence-specific DNA binding by tumor suppressor p53

1997

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“…Raghavan et al (2006) recently summarized chemical probing procedures to detect non-B DNA structures in mammalian genomic DNA using either bisulfite or KMnO 4 /OsO 4 [107]. Triplex-specific monoclonal antibodies have been developed and used to probe the conformation of H-DNA in vivo [108,109]. The triplex-specific antibodies showed significant binding to the nuclei and this binding could be inhibited by competing triplex DNA [110].…”

Section: Detecting H-dna In Vitro and In Vivomentioning

confidence: 99%

DNA triple helices: Biological consequences and therapeutic potential

Jain

Wang²,

Vásquez³

2008

Biochimie

252

197

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DNA structure is a critical element in determining its function. The DNA molecule is capable of adopting a variety of non-canonical structures, including three-stranded (i.e. triplex) structures, which will be the focus of this review. The ability to selectively modulate the activity of genes is a longstanding goal in molecular medicine. DNA triplex structures, either intermolecular triplexes formed by binding of an exogenously applied oligonucleotide to a target duplex sequence, or naturally occurring intramolecular triplexes (H-DNA) formed at endogenous mirror repeat sequences, present exploitable features that permit site-specific alteration of the genome. These structures can induce transcriptional repression and site-specific mutagenesis or recombination. Triplex-forming oligonucleotides (TFOs) can bind to duplex DNA in a sequence specific fashion with high affinity, and can be used to direct DNA-modifying agents to selected sequences. H-DNA plays important roles in vivo and is inherently mutagenic and recombinogenic, such that elements of the H-DNA structure may be pharmacologically exploitable. In this review we discuss the biological consequences and therapeutic potential of triple helical DNA structures. We anticipate that the information provided will stimulate further investigations aimed toward improving DNA triplexrelated gene targeting strategies for biotechnological and potential clinical applications.

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“…A Triplex-specific Antibody Binds to bcl-2 Mbr-To independently test for triplex character at the bcl-2 Mbr, we used monoclonal antibodies that are known to bind triplex DNA but do not bind single-stranded or double-stranded DNA (33,34). The Jel466 antibody has a binding preference for GC-rich triplexes (33), whereas the Jel318 antibody has been shown to bind to AT-rich triplexes (34) (33,34).…”

Section: More Than One Non-b Conformation Exists At the Bcl-2 Mbrmentioning

confidence: 99%

“…The Jel466 antibody has a binding preference for GC-rich triplexes (33), whereas the Jel318 antibody has been shown to bind to AT-rich triplexes (34) (33,34).…”

Section: More Than One Non-b Conformation Exists At the Bcl-2 Mbrmentioning

confidence: 99%

Evidence for a Triplex DNA Conformation at the bcl-2 Major Breakpoint Region of the t(14;18) Translocation

Raghavan

Chastain

Lee

et al. 2005

Journal of Biological Chemistry

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The most common chromosomal translocation in cancer, t(14;18), occurs at the bcl-2 major breakpoint region (Mbr) in follicular lymphomas. The 150-bp bcl-2 Mbr, which contains three breakage hotspots (peaks), has a single-stranded character and, hence, a non-B DNA conformation both in vivo and in vitro. Here, we use gel assays and electron microscopy to show that a triplexspecific antibody binds to the bcl-2 Mbr in vitro. Bisulfite reactivity shows that the non-B DNA structure is favored by, but not dependent upon, supercoiling and suggests a possible triplex conformation at one portion of the Mbr (peak I). We have used circular dichroism to test whether the predicted third strand of that suggested structure can indeed form a triplex with the duplex at peak I, and it does so with 1:1 stoichiometry. Using an intracellular minichromosomal assay, we show that the non-B DNA structure formation is critical for the breakage at the bcl-2 Mbr, because a 3-bp mutation that disrupts the putative peak I triplex also markedly reduces the recombination of the Mbr. A three-dimensional model of such a triplex is consistent with bond length, bond angle, and energetic restrictions (stacking and hydrogen bonding). We infer that an imperfect purine/purine/pyrimidine (R.R.Y) triplex likely forms at the bcl-2 Mbr in vitro, and in vivo recombination data favor this as the major DNA conformation in vivo as well.

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A monoclonal antibody to triplex DNA binds to eucaryotic chromosomes

Cited by 112 publications

References 32 publications

DNA-conformation is an important determinant of sequence-specific DNA binding by tumor suppressor p53

DNA-conformation is an important determinant of sequence-specific DNA binding by tumor suppressor p53

DNA triple helices: Biological consequences and therapeutic potential

Evidence for a Triplex DNA Conformation at the bcl-2 Major Breakpoint Region of the t(14;18) Translocation

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