Cruciform DNA

Inverted repeat sequences on double-stranded DNA suggest the formation of cruciform structures.

Cruciform DNA is a form of non-B DNA, or an alternative DNA structure. The formation of cruciform DNA requires the presence of palindromes called inverted repeat sequences.[1] These inverted repeats contain a sequence of DNA in one strand that is repeated in the opposite direction on the other strand. As a result, inverted repeats are self-complementary and can give rise to structures such as hairpins and cruciforms. Cruciform DNA structures require at least a six nucleotide sequence of inverted repeats to form a structure consisting of a stem, branch point and loop in the shape of a cruciform, stabilized by negative DNA supercoiling.[1][2]

Two classes of cruciform DNA have been described: folded and unfolded. Folded cruciform structures are characterized by the formation of acute angles between adjacent arms and main strand DNA. Unfolded cruciform structures have square planar geometry and 4-fold symmetry in which the two arms of the cruciform are perpendicular to each other.[2] Two mechanisms for the formation of cruciform DNA have been described: C-type and S-type.[3] The formation of cruciform structures in linear DNA is thermodynamically unfavorable due to the possibility of base unstacking at junction points and open regions at loops.[2]

Cruciform DNA is found in both prokaryotes and eukaryotes and has a role in DNA transcription and DNA replication, double strand repair, DNA translocation and recombination. They also serve a function in epigenetic regulation along with biological implications such as DNA supercoiling, double strand breaks, and targets for cruciform-binding proteins.[4][5][6] Cruciform structures can increase genomic instability and are involved in the formation of various diseases, such as cancer and Werner's Disease.[7][8][9]

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  2. ^ a b c Shlyakhtenko LS, Potaman VN, Sinden RR, Lyubchenko YL (July 1998). "Structure and dynamics of supercoil-stabilized DNA cruciforms". Journal of Molecular Biology. 280 (1): 61–72. CiteSeerX 10.1.1.555.4352. doi:10.1006/jmbi.1998.1855. PMID 9653031.
  3. ^ Murchie AI, Lilley DM (December 1987). "The mechanism of cruciform formation in supercoiled DNA: initial opening of central basepairs in salt-dependent extrusion". Nucleic Acids Research. 15 (23): 9641–54. doi:10.1093/nar/15.23.9641. PMC 306521. PMID 3697079.
  4. ^ Horwitz MS, Loeb LA (August 1988). "An E. coli promoter that regulates transcription by DNA superhelix-induced cruciform extrusion". Science. 241 (4866): 703–5. Bibcode:1988Sci...241..703H. doi:10.1126/science.2456617. PMID 2456617.
  5. ^ Inagaki H, Ohye T, Kogo H, Tsutsumi M, Kato T, Tong M, et al. (2013-03-12). "Two sequential cleavage reactions on cruciform DNA structures cause palindrome-mediated chromosomal translocations". Nature Communications. 4 (1): 1592. Bibcode:2013NatCo...4.1592I. doi:10.1038/ncomms2595. PMID 23481400.
  6. ^ Kurahashi H, Inagaki H, Ohye T, Kogo H, Kato T, Emanuel BS (September 2006). "Palindrome-mediated chromosomal translocations in humans". DNA Repair. 5 (9–10): 1136–45. doi:10.1016/j.dnarep.2006.05.035. PMC 2824556. PMID 16829213.
  7. ^ Lu S, Wang G, Bacolla A, Zhao J, Spitser S, Vasquez KM (March 2015). "Short Inverted Repeats Are Hotspots for Genetic Instability: Relevance to Cancer Genomes". Cell Reports. 10 (10): 1674–1680. doi:10.1016/j.celrep.2015.02.039. PMC 6013304. PMID 25772355.
  8. ^ Compton SA, Tolun G, Kamath-Loeb AS, Loeb LA, Griffith JD (September 2008). "The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer". The Journal of Biological Chemistry. 283 (36): 24478–83. doi:10.1074/jbc.M803370200. PMC 2528990. PMID 18596042.
  9. ^ Stros M, Muselíková-Polanská E, Pospísilová S, Strauss F (June 2004). "High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops". Biochemistry. 43 (22): 7215–25. doi:10.1021/bi049928k. PMID 15170359.