G-quadruplex formation at the 3' end of telomere DNA inhibits its extension by telomerase, polymerase and unwinding by helicase.

Abstract:

:Telomere G-quadruplex is emerging as a promising anti-cancer target due to its inhibition to telomerase, an enzyme expressed in more than 85% tumors. Telomerase-mediated telomere extension and some other reactions require a free 3' telomere end in single-stranded form. G-quadruplex formation near the 3' end of telomere DNA can leave a 3' single-stranded tail of various sizes. How these terminal structures affect reactions at telomere end is not clear. In this work, we studied the 3' tail size-dependence of telomere extension by either telomerase or the alternative lengthening of telomere (ALT) mechanism as well as telomere G-quadruplex unwinding. We show that these reactions require a minimal tail of 8, 12 and 6 nt, respectively. Since we have shown that G-quadruplex tends to form at the farthest 3' distal end of telomere DNA leaving a tail of no more than 5 nt, these results imply that G-quadruplex formation may play a role in regulating reactions at the telomere ends and, as a result, serve as effective drug target for intervening telomere function.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Wang Q,Liu JQ,Chen Z,Zheng KW,Chen CY,Hao YH,Tan Z

doi

10.1093/nar/gkr164

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

6229-37

issue

14

eissn

0305-1048

issn

1362-4962

pii

gkr164

journal_volume

39

pub_type

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