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2015 ; 112
(14
): 4286-91
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English Wikipedia
Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration:
insights from DNA complex structures
#MMPMID25831490
Pike AC
; Gomathinayagam S
; Swuec P
; Berti M
; Zhang Y
; Schnecke C
; Marino F
; von Delft F
; Renault L
; Costa A
; Gileadi O
; Vindigni A
Proc Natl Acad Sci U S A
2015[Apr]; 112
(14
): 4286-91
PMID25831490
show ga
RecQ helicases are a widely conserved family of ATP-dependent motors with diverse
roles in nearly every aspect of bacterial and eukaryotic genome maintenance.
However, the physical mechanisms by which RecQ helicases recognize and process
specific DNA replication and repair intermediates are largely unknown. Here, we
solved crystal structures of the human RECQ1 helicase in complexes with
tailed-duplex DNA and ssDNA. The structures map the interactions of the ssDNA
tail and the branch point along the helicase and Zn-binding domains, which,
together with reported structures of other helicases, define the catalytic stages
of helicase action. We also identify a strand-separating pin, which (uniquely in
RECQ1) is buttressed by the protein dimer interface. A duplex DNA-binding surface
on the C-terminal domain is shown to play a role in DNA unwinding, strand
annealing, and Holliday junction (HJ) branch migration. We have combined EM and
analytical ultracentrifugation approaches to show that RECQ1 can form what
appears to be a flat, homotetrameric complex and propose that RECQ1 tetramers are
involved in HJ recognition. This tetrameric arrangement suggests a platform for
coordinated activity at the advancing and receding duplexes of an HJ during
branch migration.