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A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop

Paulina Wanrooij ; Jay Uhler ; Yonghong Shi ; Fredrik Westerlund (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Maria Falkenberg ; Claes M Gustafsson
Nucleic Acids Research (0305-1048). Vol. 40 (2012), 20, p. 10334-10344.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: human pif1 helicase, binding protein, transcription termination, primer, formation, strand origin, in-vitro, replication, polymerase, sequence, twinkle



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Denna post skapades 2012-12-17. Senast ändrad 2015-07-28.
CPL Pubid: 168010

 

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Institutioner (Chalmers)

Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (GU)
Institutionen för kemi- och bioteknik, Fysikalisk kemi (2005-2014)

Ämnesområden

Livsvetenskaper
Nanovetenskap och nanoteknik
Cell- och molekylärbiologi

Chalmers infrastruktur