BLM unfolds G-quadruplexes in different structural environments through different mechanisms.

Abstract:

:Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by genome-wide characterizations of gene expression of cells from BS patients. With smFRET assays, we studied the molecular mechanism of BLM-catalyzed G4 unfolding and showed that ATP is required for G4 unfolding. Surprisingly, depending on the molecular environments of G4, BLM unfolds G4 through different mechanisms: unfolding G4 harboring a 3'-ssDNA tail in three discrete steps with unidirectional translocation, and unfolding G4 connected to dsDNA by ssDNA in a repetitive manner in which BLM remains anchored at the ss/dsDNA junction, and G4 was unfolded by reeling in ssDNA. This indicates that one BLM molecule may unfold G4s in different molecular environments through different mechanisms.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Wu WQ,Hou XM,Li M,Dou SX,Xi XG

doi

10.1093/nar/gkv361

subject

Has Abstract

pub_date

2015-05-19 00:00:00

pages

4614-26

issue

9

eissn

0305-1048

issn

1362-4962

pii

gkv361

journal_volume

43

pub_type

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