d(GC) - Association of Biotechnology and Pharmacy
d(GC) - Association of Biotechnology and Pharmacy
d(GC) - Association of Biotechnology and Pharmacy
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Current Trends in <strong>Biotechnology</strong> <strong>and</strong> <strong>Pharmacy</strong><br />
Vol. 6 (2) 204-209 April 2012, ISSN 0973-8916 (Print), 2230-7303 (Online)<br />
phosphate coordinated metal ion to N-7 <strong>of</strong><br />
guanosine. It is evident from the Ahmad et.al., (28)<br />
report that the chelation via N-7 <strong>of</strong> the guanine<br />
bases <strong>and</strong> the nearest oxygen <strong>of</strong> the (PO ) 2 - groups<br />
prevail in Al-calf thymus DNA complexes. It has<br />
been reported that cytosine has no major binding<br />
site for Al. In case <strong>of</strong> Cytosine, N-1-C-6 bond <strong>of</strong><br />
projects onto or near to the ribose ring, <strong>and</strong> N-3 is<br />
directed away from the phosphate moiety there by<br />
simultaneous binding <strong>of</strong> the metal ion to phosphate<br />
<strong>and</strong> the N-3 is not feasible <strong>and</strong> will be in anti<br />
conformation (31). Evidence <strong>of</strong> base binding <strong>of</strong> Al<br />
in the present investigation is also supported based<br />
on the alterations in the CD spectra <strong>of</strong> Poly d<br />
(<strong>GC</strong>).d(<strong>GC</strong>) <strong>and</strong> Al complex, since alterations in<br />
CD spectra for DNA <strong>and</strong> polynucleotides have been<br />
observed for base – binding metals (34). The<br />
involvement <strong>of</strong> the ionic species in the interaction<br />
<strong>of</strong> DNA is also evident from its dissociation with<br />
native DNA regeneration upon treatment with<br />
EDTA. Investigations carried out on chromatin from<br />
intact nuclei <strong>of</strong> AD –affected brains <strong>of</strong>fered evidence<br />
that Al (III) markedly increased the affinity <strong>of</strong> histone<br />
H1for DNA, thus suggesting its potential ability to<br />
inhibit the correct gene expression in vivo (35). This<br />
observation is interpreted as being due to the crosslinking<br />
action <strong>of</strong> Al (III) between histones, proteins,<br />
<strong>and</strong> DNA. The relevant bonds might involve two<br />
carboxylate lig<strong>and</strong>s pending from a histone<br />
segment <strong>and</strong> a phosphate oxygen belonging to a<br />
DNA nucleotide.<br />
The ability <strong>of</strong> Al-maltol to induce Z-DNA in<br />
poly d(<strong>GC</strong>).d(<strong>GC</strong>) might be important in chromatin<br />
condensation <strong>and</strong> in altering the gene expressional<br />
pattern. It is <strong>of</strong> considerable interest as biological<br />
function is <strong>of</strong>ten correlated with the structure at the<br />
molecular level. Moreover potentially Z-DNA<br />
forming sequences are highly dispersed through<br />
the human genome (36). It has been speculated,<br />
based on immunohistochemical data, that Z-DNA<br />
is about one-seventh as abundant as B-DNA (37).<br />
In particular interest with AD, it is observed from<br />
the Human Genome Sequence that the Z-DNA<br />
conforming <strong>GC</strong> rich sequences are observed in<br />
5´ regions <strong>of</strong> AD specific genes like PS1, PS2,<br />
Govindaraju et al<br />
207<br />
<strong>and</strong> APOE (38). It is interesting to mention that<br />
some <strong>of</strong> these genes have been over expressed<br />
in AD <strong>and</strong> have significant role in AD<br />
pathogenesis. Z-DNA formation excludes<br />
nucleosome formation <strong>and</strong> could affect the<br />
placement <strong>of</strong> nucleosome formation, as well as<br />
organization <strong>of</strong> chromosomes (39) <strong>and</strong> is<br />
considered to be involved in both transcriptional<br />
activation <strong>and</strong> inactivation (Herbert <strong>and</strong> Rich, 1996).<br />
It is theoretically postulated that the guanosine base<br />
present in DNA would be more susceptible to<br />
hydroxy radical induced DNA damage if the<br />
conformation <strong>of</strong> the DNA is Z rather than B or A<br />
because <strong>of</strong> the greater exposure <strong>of</strong> the bases (40).<br />
Restriction endonucleases <strong>and</strong> methylases are<br />
incapable <strong>of</strong> cleaving their respective recognition<br />
sites in Z-DNA conformation (41).<br />
Conclusion<br />
In conclusion the <strong>GC</strong> rich regions possessing<br />
Z-DNA conformation has great relevance to gene<br />
expression <strong>and</strong> G* oxidation. These events like to<br />
throw light in underst<strong>and</strong>ing metal induced neuronal<br />
cell death in neurodegenerative disorder.<br />
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A.J. (1973). Brain aluminum distribution in<br />
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