Repetitive extragenic palindrome (REP)-associated tyrosine transposase enzymes (RAYTs) bind REP DNA domains and catalyze their cleavage. Genomic sequence analyses identify potential noncoding REP sequences associated with RAYT-encoding genes. To probe the conformational space of potential RAYT DNA binding domains, we report here spectroscopic and calorimetric measurements that detect and partially characterize the solution conformational heterogeneity of REP oligonucleotides from six bacterial species. Our data reveal most of these REP oligonucleotides adopt multiple conformations, suggesting that RAYTs confront a landscape of potential DNA substrates in dynamic equilibrium that could be selected, enriched, and/or induced via differential binding. Thus, the transposase-bound DNA motif may not be the predominant conformation of the isolated REP domain. Intriguingly, for several REPs, the circular dichroism spectra suggest guanine tetraplexes as potential alternative or additional RAYT recognition elements, an observation consistent with these REP domains being highly nonrandom, with tetraplex-favoring 5'-G and 3'-C-rich segments. In fact, the conformational heterogeneity of REP domains detected and reported here, including the formation of noncanonical DNA secondary structures, may reflect a general feature required for recognition by RAYT transposases. Based on our biophysical data, we propose guanine tetraplexes as an additional DNA recognition element for binding by RAYT transposase enzymes.

Cancer Institute of New Jersey Rutgers University New Brunswick NJ 08903

Department of Chemistry and Chemical Biology Rutgers University 610 Taylor Rd Piscataway NJ 08854

Institute of Biotechnology Academy of Sciences of the Czech Republic Videnska 1083 142 20 Prague Czech Republic

Zobrazit více v PubMed

Higgins CF. Ames GF. Barnes WM. Clement JM. Hofnung M. Nature. 1982;298:760–762. PubMed

Di Nocera PP. De Gregorio E. Rocco F. BMC Genomics. 2013;14:522. PubMed PMC

Bertels F. Rainey PB. PLoS Genet. 2011;7:e1002132. PubMed PMC

Bertels F. Rainey PB. Mobile Genet Elem. 2011;1:262–268. PubMed PMC

Gilson E. Saurin W. Perrin D. Bachellier S. Hofnung M. Nucleic Acids Res. 1991;19:1375–1383. PubMed PMC

Bachellier S. Clement JM. Hofnung M. Res Microbiol. 1999;150:627–639. PubMed

Espeli O. Moulin L. Boccard F. J Mol Biol. 2001;314:375–386. PubMed

Aranda-Olmedo I. Tobes R. Manzanera M. Ramos JL. Marques S. Nucleic Acids Res. 2002;30:1826–1833. PubMed PMC

Rocco F. De Gregorio E. Di Nocera PP. FEMS Microbiol Lett. 2010;308:185–192. PubMed

Nunvar J. Huckova T. Licha I. BMC Genomics. 2010;11:44. PubMed PMC

Chandler M. de la Cruz F. Dyda F. Hickman AB. Moncalian G. Ton-Hoang B. Nat Rev Microbiol. 2013;11:525–538. PubMed PMC

Gonzalez-Prieto C. Agundez L. Linden RM. Llosa M. Trends Biotechnol. 2013;31:305–312. PubMed

Ton-Hoang B. Siguier P. Quentin Y. Onillon S. Marty B. Fichant G. Chandler M. Nucleic Acids Res. 2012;40:3596–3609. PubMed PMC

Messing SA. Ton-Hoang B. Hickman AB. McCubbin AJ. Peaslee GF. Ghirlando R. Chandler M. Dyda F. Nucleic Acids Res. 2012;40:9964–9979. PubMed PMC

Gilson E. Bachellier S. Perrin S. Perrin D. Grimont PA. Grimont F. Hofnung M. Res Microbiol. 1990;141:1103–1116. PubMed

Nunvar J. Licha I. Schneider B. BMC Genomics. 2013;14:385. PubMed PMC

Breslauer K. J. Methods Enzymol. 1995;259:221–242. PubMed

Henry ER. Hofrichter J. Methods Enzymol. 1992;210:129–192.

Johnson WC. Methods Enzymol. 1992;210:426–447. PubMed

Gray RD. Chaires JB. Curr Protoc Nucleic Acid Chem. 2011;17 Chapter, Unit17 14. PubMed PMC

Marky LA. Breslauer K. J. Biopolym. 1987;26:1601–1620. PubMed

Bush CA. In: In Basic Principles in Nucleic Acid Chemistry. T'so POP, editor. New York: Academic; 1974. pp. 91–169.

Zuker M. Nucleic Acids Res. 2003;31:3406–3415. PubMed PMC

Kypr J. Kejnovska I. Renciuk D. Vorlickova M. Nucleic Acids Res. 2009;37:1713–1725. PubMed PMC

Karsisiotis AI. Hessari NM. Novellino E. Spada GP. Randazzo A. Webba da Silva M. Angew Chem Int Ed Engl. Vol. 50. 2011. pp. 10645–10648. PubMed

Gray DM. Biopolymers. 1974;13:2087–2102. PubMed

Poon K. Macgregor RB., Jr Biophys Chem. 2000;84:205–216. PubMed

Mergny JL. Lacroix L. Nucleic Acids Res. 1998;26:4797–4803. PubMed PMC

Bucek P. Jaumot J. Avino A. Eritja R. Gargallo R. Chem Eur J. 2009;15:12663–12671. PubMed

Kaushik M. Suehl N. Marky LA. Biophys Chem. 2007;126:154–164. PubMed

Kuo MH. Wang ZF. Tseng TY. Li MH. Hsu ST. Lin JJ. Chang TC. J Am Chem Soc. 2015;137:210–218. PubMed

Bacolla A. Wells RD. Mol Carcinog. 2009;48:273–285. PubMed

Zhao J. Bacolla A. Wang G. Vasquez KM. Cell Mol Life Sci. 2010;67:43–62. PubMed PMC

Leroy JL. Gehring K. Kettani A. Gueron M. Biochemistry. 1993;32:6019–6031. PubMed

Frank-Kamenetskii MD. Mirkin SM. Annu Rev Biochem. 1995;64:65–95. PubMed

Keniry MA. Biopolymers. 2000;56:123–146. PubMed

Völker J. Klump HH. Breslauer K. J. Proc Natl Acad Sci USA. 2008;105:18326–18330. PubMed PMC

Wells RD. Collier DA. Hanvey JC. Shimizu M. Wohlrab F. FASEB J. 1988;2:2939–2949. PubMed

Mirkin SM. Frank-Kamenetskii MD. Annu Rev Biophys Biomol Struct. 1994;23:541–576. PubMed

Gros J. Rosu F. Amrane S. De Cian A. Gabelica V. Lacroix L. Mergny JL. Nucleic Acids Res. 2007;35:3064–3075. PubMed PMC

Campbell N. Collie GW. Neidle S. Curr Protoc Nucleic Acid Chem. 2012;17:16. Chapter, Unit17. PubMed

Murchie AIH. Lilley DM. J. Methods Enzymol. 1992;211:158–180. PubMed

Miyoshi D. Karimata H. Sugimoto N. J Am Chem Soc. 2006;128:7957–7963. PubMed

Trakselis MA. Graham BW. Nature. 2012;492:195–197. PubMed

Bansal M. Kumar A. Yella VR. Curr Opin Struct Biol. 2014;25C:77–85. PubMed

Bikard D. Loot C. Baharoglu Z. Mazel D. Microbiol Mol Biol Rev. 2010;74:570–588. PubMed PMC

Ditlevson JV. Tornaletti S. Belotserkovskii BP. Teijeiro V. Wang G. Vasquez KM. Hanawalt PC. Nucleic Acids Res. 2008;36:3163–3170. PubMed PMC

Ebbinghaus SW. Gee JE. Rodu B. Mayfield CA. Sanders G. Miller DM. J Clin Invest. 1993;92:2433–2439. PubMed PMC

Belotserkovskii BP. De Silva E. Tornaletti S. Wang G. Vasquez KM. Hanawalt PC. J Biol Chem. 2007;282:32433–32441. PubMed

Siddiqui-Jain A. Grand CL. Bearss DJ. Hurley LH. Proc Natl Acad Sci USA. 2002;99:11593–11598. PubMed PMC

Broxson C. Beckett J. Tornaletti S. Biochemistry. 2011;50:4162–4172. PubMed

Kang C. Zhang XH. Ratliff R. Moyzis R. Rich A. Nature. 1992;356:126–131. PubMed

Ahmed S. Henderson E. Nucleic Acids Res. 1992;20:507–511. PubMed PMC

Kendrick S. Kang HJ. Alam MP. Madathil MM. Agrawal P. Gokhale V. Yang D. Hecht SM. Hurley LH. J Am Chem Soc. 2014;136:4161–4171. PubMed PMC

Han H. Hurley LH. Trends Pharmacol Sci. 2000;21:136–142. PubMed

Lam EY. Beraldi D. Tannahill D. Balasubramanian S. Nat Commun. 2013;4:1796. PubMed PMC

Gray LT. Vallur AC. Eddy J. Maizels N. Nat Chem Biol. 2014;10:313–318. PubMed PMC

Todd AK. Neidle S. Nucleic Acids Res. 2011;39:4917–4927. PubMed PMC

Burge S. Parkinson GN. Hazel P. Todd AK. Neidle S. Nucleic Acids Res. 2006;34:5402–5415. PubMed PMC

Bochman ML. Paeschke K. Zakian VA. Nat Rev Genet. 2012;13:770–780. PubMed PMC

Lexa M. Kejnovsky E. Steflova P. Konvalinova H. Vorlickova M. Vyskot B. Nucleic Acids Res. 2014;42:968–978. PubMed PMC

Neidle S. Read MA. Biopolymers. 2000;56:195–208. PubMed

Wei D. Todd AK. Zloh M. Gunaratnam M. Parkinson GN. Neidle S. J Am Chem Soc. 2013;135:19319–19329. PubMed

Conformation-based refinement of 18-mer DNA structures

Structural variability of CG-rich DNA 18-mers accommodating double T-T mismatches