Mechanisms of DNA bending

Current Opinion in Chemical Biology

Volumn 2, Issue 6, 1998, Pages 688-694

  Maher III, L James ^a  

^a MAYO GRADUATE SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA;

ANIMAL; CHEMISTRY; CONFORMATION; CRYSTALLIZATION; HUMAN; REVIEW;

ANIMALS; CRYSTALLIZATION; DNA; HUMANS; NUCLEIC ACID CONFORMATION;

EID: 0032246262     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(98)80104-X     Document Type: Article

References (41)

1. Trun NJ, Marko JF: Architecture of a bacterial chromosome. Am Soc Microbiol News 1998, 64:276-283.
2. Liu-Johnson H-N, Gartenberg M, Crothers DM: The DNA binding domain and bending angle of E. coli CAP protein. Cell 1986, 47:995-1005.
3. Werner MH, Groneborn AM, Clore GM: Intercalation, DNA kinking and the control of transcription. Science 1996, 271:778-784.
4. Werner MH, Burley SK: Architectural transcription factors: proteins that remodel DNA. Cell 1997, 88:733-736.
5. Schultz SC, Shields GC, Steitz TA: Crystal structure of a CAP-DNA complex: the DNA is bent by 90°. Science 1991, 253:1001-1007.
6. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ: Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 1997, 389:251-260. This paper has been accurately described as a 'tour de force' of biochemistry, involving full reconstitution of the histone octamer from recombinant proteins. The unprecedented resolution of this nucleosome structure permits a full accounting of protein-DNA contacts, and makes predictions about the kinds of forces that give rise to the dramatic DNA bending observed.
7. Parkinson G, Wilson C, Gunasekera A, Ebright YW, Ebright RE, Berman HM: Structure of the CAP-DNA complex at 2.5 Å resolution: a complete picture of the protein-DNA interface. J Mol Biol 1996, 260:395-408.
8. Pio F, Kodandapani R, Ni CZ, Shepard W, Klemsz M, McKercher SR, Maki RA, Ely KR: New insights on DNA recognition by ets proteins from the crystal structure of the PU.1 ETS domain DNA complex. J Biol Chem 1996, 271:23329-23337.
9. Tan S, Richmond TJ: Crystal structure of the yeast MATα2/MCM1/DNA ternary complex. Nature 1998, 391:660-666.
10. Dickerson RE: DNA bending: the prevalence of kinkiness and the virtues of normality. Nucleic Acids Res 1998, 26:1906-1926. This paper provides a comprehensive survey of bent DNA structures extracted from 86 complexes involving sequence-specific proteins. Several useful summary statistics and diagrammatic representations are introduced. Three categories of DNA bending are discerned, with the interesting observation that base pair tilt is never a significant component of DNA bending. This summary is uniquely comprehensive.
11. Hagerman PJ: Do basic region-leucine zipper proteins bend their DNA targets ... does it matter? Proc Natl Acad Sci USA 1996, 93:9993-9996.
12. McGill G, Fisher D: DNA bending and the curious case of Fos/Jun. Chem Biol 1998, 5:29-38. This brief review paper is particularly helpful in its diagrammatic summaries of various DNA bending assays. The authors provide useful background and a description of the ongoing debate concerning DNA bending by basicleucine zipper proteins.
13. Kerppola TK: Fos and Jun bend the AP-1 site: effects of probe geometry on the detection of protein-induced DNA bending. Proc Natl Acad Sci USA 1996, 93:10117-10122.
14. Kerppola T: Comparison of DNA bending by Fos-Jun and phased A tracts by multifactorial phasing analysis. Biochemistry 1997, 36:10872-10884. The author presents a comprehensive analysis of variables influencing electrophoretic phasing experiments. Among the contributions of this work are the introduction of a damped harmonic oscillation function for curvefitting of phasing data. In the context of the debate concerning DNA bending by basic-leucine zipper (bZIP) proteins, the author uses intrinsically curved A tracts to argue for three criteria to establish actual DNA bending, and presents evidence that the phasing properties of bZIP proteins meet these criteria.
15. Kerppola TK, Curran T: The transcription activation domains of Fos and Jun induce DNA bending through electrostatic interactions. EMBO J 1997, 16:2907-2916. Using electrophoretic phasing experiments, the authors explore an impressive number of combinations of protein domains from Jun and Fos proteins to explore which protein domains contribute to phasing anomalies consistent with DNA bending. It is argued that, although they are distant from the DNA binding domains, the anionic transcription activation domains of these basic-leucine zipper proteins can also influence DNA bending through electrostatic effects. These bending effects are argued to deflect the DNA gently away from the transcription activation domain of the bound protein. The authors suggest that the opposite directions of apparent DNA bending by Fos and Jun are related to the opposite disposition of the acidic transcription activation domains in these proteins.
16. Leonard D, Rajaram N, Kerppola T: Structural basis of DNA bending and oriented heterodimer binding by the basic leucine zipper domains of Fos and Jun. Proc Natl Acad Sci USA 1997, 94:4913-4918.
17. Sitlani A, Crothers DM: Fos and Jun do not bend the AP-1 recognition site. Proc Natl Acad Sci USA 1996, 93:3248-3252.
18. •]), so there is, in fact, no disagreement between the groups on this point. It will therefore be important to extend the minicircle competition assays to other basic-leucine zipper combinations thought to bend DNA more dramatically.
19. Elcock AH, McCammon JA: The low dielectric interior of proteins is sufficient to cause major structural changes in DNA on association. J Am Chem Soc 1996,118:3787-3788.
20. Travers AA: Reading the minor groove. Nat Struct Biol 1995, 2:615-618.
21. Crothers DM: Upsetting the balance of forces in DNA. Science 1994, 266:1819-1820.
22. Strauss JK, Maher LJ: DNA bending by asymmetric phosphate neutralization. Science 1994, 266:1829-1834.
23. Strauss-Soukup JK, Rodrigues PD, Maher LJ: Effect of base composition on DNA bending by phosphate neutralization. Biophys Chem 1998, in press. This paper employs electrophoretic assays of DNA duplexes ligated end-to-end to explore how DNA base composition affects DNA bending by asymmetric phosphate neutralization. Patterns of six phosphate groups are neutralized, three consecutive phosphate groups on each side of one minor groove of DNA, and DNA bending is monitored in GC- versus AT-rich contexts. Perhaps surprisingly, induced DNA bending (∼20°) was comparable in both cases, suggesting little difference in the intrinsic minor groove compressibilities of the two sequences studied.
24. p stereoisomers) distort DNA structure to a small extent by nonelectrostatic effects, but that electrostatic effects remain a plausible explanation for induced DNA bending by asymmetric methylphosphonate substitutions.
25. Manning GS, Ebralidse KK, Mirzabekov AD, Rich A: An estimate of the extent of folding of nucleosomal DNA by laterally asymmetric neutralization of phosphate groups. J Biomol Struct Dyn 1989, 6:877-889.
26. Sanghani SR, Zakrzewska K, Lavery R: Modeling DNA bending induced by phosphate neutralisation. In Ninth Conversation in Biomolecular Stereodynamics. Edited by Sarma RH, Sarma MH. Schenectady: Adenine Press;1996: 267-278.
27. Strauss-Soukup JK, Maher LJ: Role of asymmetric phosphate neutralization in DNA bending by PU.1. J Biol Chem 1997, 272:31570-31575. This paper applies the predictions of asymmetric phosphate neutralization to the case of an actual DNA-protein complex for which high-resolution structural data are known. In the X-ray crystal structure, PU.1 protein gently bends DNA (∼8°) as it contacts one face of the double helix, making asymmetric salt bridges to DNA phosphates. The shape of the unbound DNA site was determined by electrophoretic analysis before and after neutralization of the relevant phosphate groups by methylphosphonate substitution. DNA bending induced by charge neutralization (∼28°) is larger than observed for protein binding, and is in a similar direction.
28. Strauss-Soukup J, Maher L: Electrostatic effects in DNA bending by GCN4 mutants. Biochemistry 1998, 37:1060-1066. Electrophoretic phasing analyses are used to explore the consequences of modifying the basic-leucine zipper region of the DNA binding protein GCN4 (which does not itself appear to bend DNA) to include various numbers of anionic or cationic amino acid residues just amino-terminal to the basic region that contacts DNA. The amplitude of the electrophoretic anomaly in all cases is proportional to the net charge of the amino terminus of the protein. Moreover, the direction of apparent DNA bending is as might be expected from simple electrostatic considerations - toward the cationic domain, and away from the anionic domain. Alternative explanations for these data include the possibility that local amino acid charges cause phase-dependent changes in the interaction of the complex with the gel matrix, or in the rigidity of the complex.
29. ••], the authors have chemically neutralized phosphates near sites of possible contact with cationic amino acids of GCN4 derivatives in the AP-1 DNA sequence thought to be bent upon protein binding. The extent of phosphate neutralization correlates well in both quantitative and qualitative terms with the results of electrophoretic phasing experiments involving binding of GCN4 derivatives with various numbers of amino-terminal cationic amino acid residues.
30. Kerppola TK, Curran T: Selective DNA bending by a variety of bZIP proteins. Mol Cell Biol 1993, 13:5479-5489.
31. Paolella D, Liu Y, Fabian M, Schepartz A: Electrostatic mechanism for DNA bending by bZIP proteins. Biochemistry 1997, 36:10033-10038. Electrophoretic phasing analyses and chemical phosphate neutralization experiments are used to demonstrate that, consistent with an asymmetric phosphate neutralization model for DNA bending, basic-leucine zipper (bZIP) peptide derivatives with cationic amino acid substitutions just aminoterminal to the basic region influence the apparent shape of DNA bound at the CREB responsive element (CRE) sequence. Intrinsically curved CRE DNA is straightened by certain bZIP proteins, and neutralization of two symmetry-related phosphate groups flanking the DNA minor groove (on the DNA face opposite to the leucine zipper of the protein) is shown to be correlated to this effect.
32. Strauss-Soukup JK, Maher LJ: DNA bending by GCN4 mutants bearing cationic residues. Biochemistry 1997, 36:10026-10032.
33. Metallo S, Paolella D, Schepartz A: The role of a basic amino acid cluster in target site selection and non-specific binding of bZIP peptides to DNA. Nucleic Acids Res 1997, 25:2967-2972.
34. Strauss JK, Roberts C, Nelson MG, Switzer C, Maher LJ: DNA bending by hexamethylene-tethered ammonium ions. Proc Natl Acad Sci USA 1996, 93:9515-9520.
35. Strauss JK, Prakash TP, Roberts C, Switzer C, Maher LJ: DNA bending by a phantom protein. Chem Biol 1996, 3:671-678.
36. 4+. Using this interesting approach, the authors demonstrated that the DNA persistence length is in the expected range of 450-500 Å in monovalent salt, but is substantially reduced to 250-300 Å by multivalent cations. The authors make a convincing case for the utility of single-molecule methods for studying physical properties of DNA.
37. •], the authors approach the problem of how multivalent cations reduce the persistence length of duplex DNA below that achieved under high monovalent salt conditions. An electrostatic mechanism is proposed in which multivalent cations transiently occupy sites within the DNA major groove, electrostatically repelling sodium counterions from neighboring phosphate groups. According to this mechanism, the differential unscreening of local phosphate groups would lead them to be highly attracted to the multivalent cation, generating a transient bend toward of the major groove of ∼20-40°. The number of multivalent cations positioned to induce such bends is thought to be small, because only cations with particularly strong electrostatic interactions will persist at the major groove site with a lifetime comparable to the time required for DNA bending.
38. Liberles DA, Dervan PB: Design of artificial sequence-specific DNA bending ligands. Proc Natl Acad Sci USA 1996, 93:9510-9514.
39. Akiyama T, Hogan ME: Microscopic DNA flexibility analysis - probing the base composition and ion dependence of minor groove compression with an artificial DNA bending agent. J Biol Chem 1996, 271:29126-29135.
40. Akiyama T, Hogan ME: The design of an agent to bend DNA. Proc Natl Acad Sci USA 1996, 93:12122-12127.
41. Akiyama T, Hogan ME: Structural analysis of DNA bending induced by tethered triple helix forming oligonucleotides. Biochemistry 1997, 36:2307-2315.