Archaeal Hel308 helicase targets replication forks in vivo and in vitro and unwinds lagging strands.

Abstract:

:Mutations in mammalian and Drosophila Hel308 and PolQ paralogues cause genome instability but their helicase functions are mysterious. By in vivo and in vitro analysis, we show that Hel308 from archaea (Hel308a) may act at stalled replication forks. Introducing hel308a into Escherichia coli dnaE strains that conditionally accumulate stalled forks caused synthetic lethality, an effect indistinguishable from E.coli RecQ. Further analysis in vivo indicated that the effect of hel308a is exerted independently of homologous recombination. The minimal biochemical properties of Hel308a protein were the same as human Hel308. We describe how helicase actions of Hel308a at fork structures lead specifically to displacement of lagging strands. The invading strand of D-loops is also targeted. Using archaeal Hel308, we propose models of action for the helicase domain of PolQ, promoting loading of the translesion polymerase domain. We speculate that removal of lagging strands at stalled forks by Hel308 promotes the formation of initiation zones, priming restart of lagging strand synthesis.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Guy CP,Bolt EL

doi

10.1093/nar/gki685

keywords:

subject

Has Abstract

pub_date

2005-06-30 00:00:00

pages

3678-90

issue

11

eissn

0305-1048

issn

1362-4962

pii

33/11/3678

journal_volume

33

pub_type

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