ALTERNATIVE FORMS OF DNA EXIST

Written Report in Genetics Lecture

Jeremaine T. Sajul BS BIO 4-2

Local structural transitions from the common B-DNA conformation into other DNA forms
can be functionally important. The formation of non-B-DNA within certain sequence elements of
DNA can be induced by changes in environmental conditions, protein binding and superhelical
tension. Several lines of evidence indicate that alternative DNA structures exist in prokaryotic
and eukaryotic cells. The data on their involvement in replication, gene expression,
recombination and mutagenesis continues to accumulate.
The formation of alternative DNA secondary structures can result in DNA breakage
leading to cancer and other diseases. Chromosomal fragile sites, which are regions of the
genome that exhibit chromosomal breakage under conditions of mild replication stress, are
predicted to form stable DNA secondary structures. DNA breakage at fragile sites is associated
with regions that are deleted, amplified or rearranged in cancer. Despite the correlation,
unbiased examination of the ability to form secondary structures has not been evaluated in
fragile sites.

Comparison Geometries of the Most Common DNA Forms

Side view of A-, B-, and Z-DNA.

The helix axis of A-, B-, and Z-DNA.

Geometry attribute:

A-form

B-form

Z-form

Helix sense

right-handed

right-handed

left-handed

Repeating unit

1 bp

1 bp

2 bp

Rotation/bp

33.6

35.9

60/2

Mean bp/turn

11

10.5

12

1.2

Inclination of bp to axis +19

Rise/bp along axis

2.4 (0.24 nm) 3.4 (0.34 nm) 3.7 (0.37 nm)

Rise/turn of helix

24.6 (2.46 nm) 33.2 (3.32 nm) 45.6 (4.56 nm)

Mean propeller twist

+18

+16

Glycosyl angle

anti

anti

pyrimidine: anti,
purine: syn

Sugar pucker

C3'-endo

C2'-endo

C:
C2'-endo,
G: C2'-exo

Diameter

23 (2.3 nm)

20 (2.0 nm)

18 (1.8 nm)

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA
forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms.
The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount
and direction of supercoiling, chemical modifications of the bases, the type and concentration of
metal ions, as well as the presence of polyamines in solution.
The first published reports of A-DNA X-ray diffraction patterns and also B-DNA
used analyses based on Patterson transforms that provided only a limited amount of structural
information for oriented fibers of DNA. An alternate analysis was then proposed by Wilkins et
al., in 1953, for the in vivo B-DNA X-ray diffraction/scattering patterns of highly hydrated DNA
fibers in terms of squares of Bessel functions. In the same journal, James Watson and Francis
Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to
suggest that the structure was a double-helix.
Although the "B-DNA form" is most common under the conditions found in cells, it is not
a well-defined conformation but a family of related DNA conformations that occur at the high
hydration levels present in living cells. Their corresponding X-ray diffraction and scattering
patterns are characteristic of molecular paracrystals with a significant degree of disorder.

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide
minor groove and a narrower, deeper major groove. The A form occurs under non-physiological
conditions in partially dehydrated samples of DNA, while in the cell it may be produced in hybrid
pairings of DNA and RNA strands, as well as in enzyme-DNA complexes. Segments of DNA
where the bases have been chemically modified by methylation may undergo a larger change in
conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed
spiral, the opposite of the more common B form.[49] These unusual structures can be recognized
by specific Z-DNA binding proteins and may be involved in the regulation of transcription.

References:

Hum Mol Genet. 2013 Apr 1;22(7):1443-56. doi: 10.1093/hmg/dds561. Epub 2013 Jan 7.
Role of DNA secondary structures in fragile site breakage along human chromosome 10.
Dillon LW, Pierce LC, Ng MC, Wang YH.
Source
Department of Biochemistry, Wake Forest School of Medicine, Medical Center Boulevard,
Winston-Salem, NC 27157-1016, USA.
Madame Curie Bioscience Database [Internet].
DNA: Alternative Conformations and Biology
Vladimir N. Potaman and Richard R. Sinden.