Resolution of the Holliday junction recombination intermediate by human GEN1 at the single-molecule level.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
28 02 2019
28 02 2019
Historique:
accepted:
13
12
2018
revised:
19
11
2018
received:
11
09
2018
pubmed:
28
12
2018
medline:
28
8
2019
entrez:
28
12
2018
Statut:
ppublish
Résumé
Human GEN1 is a cytosolic homologous recombination protein that resolves persisting four-way Holliday junctions (HJ) after the dissolution of the nuclear membrane. GEN1 dimerization has been suggested to play key role in the resolution of the HJ, but the kinetic details of its reaction remained elusive. Here, single-molecule FRET shows how human GEN1 binds the HJ and always ensures its resolution within the lifetime of the GEN1-HJ complex. GEN1 monomer generally follows the isomer bias of the HJ in its initial binding and subsequently distorts it for catalysis. GEN1 monomer remains tightly bound with no apparent dissociation until GEN1 dimer is formed and the HJ is fully resolved. Fast on- and slow off-rates of GEN1 dimer and its increased affinity to the singly-cleaved HJ enforce the forward reaction. Furthermore, GEN1 monomer binds singly-cleaved HJ tighter than intact HJ providing a fail-safe mechanism if GEN1 dimer or one of its monomers dissociates after the first cleavage. The tight binding of GEN1 monomer to intact- and singly-cleaved HJ empowers it as the last resort to process HJs that escape the primary mechanisms.
Identifiants
pubmed: 30590761
pii: 5258024
doi: 10.1093/nar/gky1280
pmc: PMC6393306
doi:
Substances chimiques
DNA, Cruciform
0
Endodeoxyribonucleases
EC 3.1.-
GEN1 protein, human
EC 3.1.21.-
Holliday Junction Resolvases
EC 3.1.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1935-1949Informations de copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.
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