DNA Structure and Gene Regulation

Wells, Robert D.; Goodman, Thomas C.; Hillen, Wolfgang; Horn, Glenn T.; Klein, Ronald D.; Larson, Jacquelynn E.; Müller, Ulrich; Neuendorf, S.K.; Panayotatos, Nikos; Stirdivant, Steven M.

doi:10.1016/s0079-6603(08)60674-1

Cited by 198 publications

(46 citation statements)

References 351 publications

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“…Misaligned structures are not favored in double-stranded DNA but can be expected in single-stranded or supercoiled DNA. Thus, the formation of a DNA hairpin is likely to depend not only upon its intrinsic hydrogen bonding potential but also upon CLC ACC CAC;C;Ci CA TC[ T the processes that influence the formation of single-stranded or supercoiled intermediates (19). These processes are likely to include many aspects of DNA replication, recombination, and repair.…”

Section: Discussionmentioning

confidence: 99%

Structural intermediates of deletion mutagenesis: a role for palindromic DNA.

Glickman¹,

Ripley²

1984

Proc. Natl. Acad. Sci. U.S.A.

213

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A model is presented for deletion mutations whose formation is mediated by palindromic and quasipalindromic DNA sequences. It proposes that the self-complementarity of palindromes allows the formation of DNA secondary structures that serve as deletion intermediates. The structures juxtapose the end points of the deletion and thus direct deletion specificity. While misaligned DNA intermediates that explain deletion termini occurring in repeated DNA sequences have been described, no explanations have been offered for deletion termini occurring in other sequences. The DNA secondary structures whose formation is mediated by palindromic sequences appear to explain many of these. In this paper, secondary-structure intermediates are described for a series of spontaneous deletions of known sequence in the lad gene of Escherichia coli. The model is supported by its failure to predict structures that can juxtapose simulated deletion termini in the lacI gene. We have found a strong association between palindromic sequences and repeated sequences at lacl deletion termini that suggests the joint participation of repeated and palindromic DNA sequences in the formation of some deletions. Sequences of deletions in other organisms also suggest the participation of palindromic DNA sequences in the formation of deletions.Local DNA sequences can strongly influence the frequency of mutation (1). The frequent association of deletion termini with repeated DNA sequences (2-4) suggests that deletion mutations are no exception. The In its simplest form, our model proposes that DNA secondary structures whose formation is potentiated by palindromic or quasipalindromic DNA sequences participate in deletion formation through the juxtaposition of deletion end points. The inherent self-complementarity of palindromic DNA sequences permits the formation of cruciform or hairpin structures in nucleic acids, precisely juxtaposing otherwise distant bases (6). Repeated DNA sequences are not required.The termini of the E. coli lacd deletion S86 cannot be juxtaposed by a misalignment involving repeated sequences. However, the deletion termini are located precisely at the ends of a quasipalindromic DNA sequence that includes the entire deletion. The formation of a DNA hairpin or cruciform structure in the wild-type DNA sequence places the deletion termini immediately adjacent to one another, rather than separated by their normal linear distance of 27 base pairs (Fig. 1A). This structural intermediate would produce the S86 deletion if it served as a substrate for excision or as a template for DNA synthesis (Fig. 1B). The latter process might be mediated by either DNA polymerase or DNA ligase. A ligation across such a hairpin stem might also be responsible for deletions if the hairpin served as a substrate for nucleases that removed aberrantly aligned regions from ordinary double-stranded DNA. Whatever the precise molecular mechanism(s) responsible for the production of deletions from such DNA structures, the prediction of the model is that the ...

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Section: Discussionmentioning

confidence: 99%

Structural intermediates of deletion mutagenesis: a role for palindromic DNA.

Glickman¹,

Ripley²

1984

Proc. Natl. Acad. Sci. U.S.A.

213

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“…The role of DNA structure in gene regulation has been stressed repeatedly (e.g., Wells et al, 1980;Jovin, 1976 (Wachsman and Anthony, 1980, and …”

Section: Discussionmentioning

confidence: 99%

Z* DNA, the left-handed helical form of poly[d(G-C)] in MgCl2-ethanol, is biologically active.

Sande¹,

Jovin²

1982

The EMBO Journal

164

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The interconversion between the right (R) and left (L) helical forms of poly [d(G-C)] occurs at low concentrations of MgCI2 and EtOH, acting together in a highly synergistic manner. established by X-ray crystallography (Wang et al., 1979;Drew et al., 1980). However, L DNA formed in Mg2+-EtOH (which we designate as Z* DNA) has unique properties: a) it can be sedimented readily out of solution at low speed, indicative of condensation and intermolecular aggregation; b) it supports the binding of several intercalating (ethidium bromide, actinomycin D) and non-intercalating (mithramycin) drugs, although these interact preferentially with the R (i.e., B) form of DNA; and c) it functions as a template for Escherichia coli RNA polymerase. B and Z* DNAs can be generated under idential ionic conditions and compared in a number of biochemical systems. Our results suggest that left-handed DNA may form under physiological conditions and serve a biological function.

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“…Although at the present time we do not fully understand the factors associated with the cooperativity and allosterism observed in these and other systems, (e.g., the possible role of satellite DNA, etc. ), it is likely that the phenomena which are responsible for the cooperative type binding isotherms are important in the 8221 area of DNA structure and function (30), as well as the in vivo activity of these compounds.…”

Section: Sc Photometric Analmentioning

confidence: 99%