A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop
Artikel i vetenskaplig tidskrift, 2012

In human mitochondria the transcription machinery generates the RNA primers needed for initiation of DNA replication. A critical feature of the leading-strand origin of mitochondrial DNA replication is a CG-rich element denoted conserved sequence block II (CSB II). During transcription of CSB II, a G-quadruplex structure forms in the nascent RNA, which stimulates transcription termination and primer formation. Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. We here demonstrate that the unusual behavior of the RNA primer is explained by the formation of a stable G-quadruplex structure, involving the CSB II region in both the nascent RNA and the non-template DNA strand. Based on our data, we suggest that G-quadruplex formation between nascent RNA and the non-template DNA strand may be a regulated event, which decides the fate of RNA primers and ultimately the rate of initiation of DNA synthesis in human mitochondria.

primer

human pif1 helicase

formation

transcription termination

sequence

polymerase

strand origin

replication

binding protein

in-vitro

twinkle

Författare

Paulina Wanrooij

Göteborgs universitet

Jay Uhler

Göteborgs universitet

Yonghong Shi

Göteborgs universitet

Fredrik Westerlund

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

Maria Falkenberg

Göteborgs universitet

Claes M Gustafsson

Göteborgs universitet

Nucleic Acids Research

0305-1048 (ISSN) 1362-4962 (eISSN)

Vol. 40 10334-10344

Styrkeområden

Nanovetenskap och nanoteknik

Livsvetenskaper och teknik

Ämneskategorier

Biokemi och molekylärbiologi

DOI

10.1093/nar/gks802