Different researches shows that, g-quadruplex- kind of tandem repeats are present in vivo, Telomeres having tandem repeats of d(TTAGGG) , herein G is either anti or sync. 5’- UTR (untranslated region) of mRNA (U–U–U–U tetrads, as well as G- and U-containing octads) Promoter region of c-myc , c-kit and variant bcl-2 oncogenes. inferior oncogenic expression & veiled binding target of telomere associated proteins ( TRF1, POT1) may help to combat the uncontrolled cellular growth by inducing apoptosis & inhibit the telomerase overactivity.

1. Telomere & Cancer
By : Moumita Basak
PG(Pharmacology)
GNIPST
2015-2017

2. SN: CANCER
1. Uncontrolled & immature cell proliferation.
2. Can be caused by one of the followings:
a) Transformation of proto-oncogene to Oncogene.
b) Reduced activity of Tumour suppressor gene.
c) Decreased Apoptotic function.
colorectal cancer
metstasis

3. SN: Telomere
1. The very end part of chromosome containing Tandem
repeats (d(TTAGGG)), rich in guanine residues which is also
known to maintain the genomic integrity.
2. Only in early embryonic cell & stem cell it is synthesized by
an enzyme, Telomerase( own RNA primer & RNA dependent
DNA polymerase) which is only present in above cells.
3. Thus, in absence of telomerase, during end replication
problem, the 3’-overhang in each DNA i.e. telomeric segment
can’t be replicated by normal pathway in somatic cell.
4. Hence at each cell cycle, the length of this region shortens
which ultimately triggers the genomic instability, senescence &
apoptosis if it reaches critical inferiority.

4. Telomeric repeat binding factor 1 (TRF1), TRF2.
Repressor-activator protein 1 (RAP1),
Protection of telomeres protein 1 (POT1),
TIN2 organizing protein (TPP1), and TIN2.
The reverse transcriptase catalytic subunit
(TERT) and the telomerase RNA component (TERC).
POT1 binds to the 3’- singled-
stranded overhang of the DNA
repeats.
TRF1 and TRF2 bind to telomeric
double-stranded DNA

5. !!MissingLinkbetweenCancer & Telomer!!
 Although Normal somatic cell can’t but the
Cancerous cells are that much capable to
express Telomerase, thus in each cell cycle
cancerous cells are capable to maintain genomic
integrity by synthesizing the Telomer.
 As a result the cancerous cells get a kind of
immortality which is unusual.
Thus, we may conclude the missing link is
supposed to be the Telomerase expression.

6. Possible New horizon of Anticancer Activity
1. Anti telomerase activity
2. Inhibition of interaction between telomere &
telomerase.
Among above these 2 possibilities, the second one is
shown by specific few group of chemical entity by
stabilizing quadruplex which is found at
a. Promoter region of the Oncogenes i.e. c-kit, c-
myc, bcl2 variant genes.
b. Telomeric 3’- overhang containing G tandem
repeat.
c. 5’- UTR of mRNA responsible for post
transcriptional modification
 Inhibition of transcription & disability of telomerase may
induce APOPTOSIS, which can be a defense against
uncontrolled growth of the cancerous cells.

7. ??G-Quadruplex??
 As per, WC model, DNA is
self complementary, duplex
stabilized by H bond
between A=T, G≡C.
 But, at physiological pH, at a
specific concentration of Na+ & K+
DNA can form tetraplex structure for
which G rich regions are required.
 Here, 4 ‘G’ form tetrad by hoogsten
H bond & then get stacked over each
other to form G-quadruplex or
tetraplex.
In this form no enzyme can
interact with the DNA, which
induce Genomic Instability i.e.
Apoptosis.

8. Drugs showing G-quadruplex Stabilizing Action
1) 2,6-Diamido anthraquinones (BSU1051)
2) Cationic porphyrins (TMPyP4)
3) Perylenes (PIPER)
4) Isoquinoline Alkaloids ( Berberine,
Sanguinarine)
5) Indole derivative ( Indirubin)
6) Isoflavonoid ( Daidzein. Genistein)

9. REFERENCES
1. Haiyong Han and Laurence H. Hurley; “G-quadruplex DNA: a
potential target
for anti-cancer drug design”; Arizona Cancer Center.
2. Yun-Xia Xiong, Hua-Fei Su1, Peng Lv, Yan Ma, Shi-Ke Wang ;
“A newly identified berberine derivative induces cancer cell
senescence by stabilizing endogenous G-quadruplexes and sparking a
DNA damage response at the telomere region” ; Oncotarget; Sept, 2015
3. .Stephen Neidle; Human telomeric G-quadruplex: The current status of telomeric G-
quadruplexes as therapeutic targets in human cancer; The febs journal; doi:10.1111/j.1742-
4658.2009.07463.x; OCT, 2009
4. Molecular Cell Biology by Lodish, Berk,Matsudaira. 5th edition.