MOC1 cleaves Holliday junctions through a cooperative nick and counter-nick mechanism mediated by metal ions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 Jun 2024
17 Jun 2024
Historique:
received:
21
08
2023
accepted:
06
06
2024
medline:
18
6
2024
pubmed:
18
6
2024
entrez:
17
6
2024
Statut:
epublish
Résumé
Holliday junction resolution is a crucial process in homologous recombination and DNA double-strand break repair. Complete Holliday junction resolution requires two stepwise incisions across the center of the junction, but the precise mechanism of metal ion-catalyzed Holliday junction cleavage remains elusive. Here, we perform a metal ion-triggered catalysis in crystals to investigate the mechanism of Holliday junction cleavage by MOC1. We capture the structures of MOC1 in complex with a nicked Holliday junction at various catalytic states, including the ground state, the one-metal ion binding state, and the two-metal ion binding state. Moreover, we also identify a third metal ion that may aid in the nucleophilic attack on the scissile phosphate. Further structural and biochemical analyses reveal a metal ion-mediated allosteric regulation between the two active sites, contributing to the enhancement of the second strand cleavage following the first strand cleavage, as well as the precise symmetric cleavage across the Holliday junction. Our work provides insights into the mechanism of metal ion-catalyzed Holliday junction resolution by MOC1, with implications for understanding how cells preserve genome integrity during the Holliday junction resolution phase.
Identifiants
pubmed: 38886375
doi: 10.1038/s41467-024-49490-9
pii: 10.1038/s41467-024-49490-9
doi:
Substances chimiques
DNA, Cruciform
0
Metals
0
Holliday Junction Resolvases
EC 3.1.21.-
Saccharomyces cerevisiae Proteins
0
Ions
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5140Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31971222
Informations de copyright
© 2024. The Author(s).
Références
Science. 2016 Jun 10;352(6291):1334-7
pubmed: 27284197
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6498-502
pubmed: 8341661
Mol Cell Biol. 1997 Nov;17(11):6465-71
pubmed: 9343409
Phys Chem Chem Phys. 2020 Jan 21;22(3):1534-1542
pubmed: 31872818
Genes Dev. 1999 Jul 15;13(14):1861-70
pubmed: 10421637
Nat Chem Biol. 2019 Mar;15(3):269-275
pubmed: 30664685
Proc Natl Acad Sci U S A. 1985 Nov;82(21):7247-51
pubmed: 3903750
EMBO J. 2006 May 3;25(9):1924-33
pubmed: 16601679
Cell Rep. 2015 Dec 22;13(11):2565-2575
pubmed: 26686639
J Biol Chem. 1987 Sep 15;262(26):12752-8
pubmed: 3305513
Cell. 2009 Jul 10;138(1):63-77
pubmed: 19596235
Cold Spring Harb Perspect Biol. 2014 Sep 02;6(9):a023192
pubmed: 25183833
Elife. 2015 Dec 18;4:
pubmed: 26682650
Nature. 2012 Jul 11;487(7406):196-201
pubmed: 22785315
Nucleic Acids Res. 2019 Dec 16;47(22):11681-11690
pubmed: 31584081
Nat Struct Mol Biol. 2018 Aug;25(8):715-721
pubmed: 30076410
Methods Enzymol. 1997;276:307-26
pubmed: 27754618
Science. 2004 Jun 18;304(5678):1822-6
pubmed: 15205536
Genet Res. 2007 Dec;89(5-6):285-307
pubmed: 18976517
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8873-8
pubmed: 10430863
J Mol Biol. 2014 Dec 12;426(24):3946-3959
pubmed: 25315822
Nature. 2008 Nov 20;456(7220):357-61
pubmed: 19020614
Mol Cell Biol. 2005 Sep;25(17):7569-79
pubmed: 16107704
PLoS One. 2009;4(4):e5347
pubmed: 19399178
Cell. 2009 Jul 10;138(1):78-89
pubmed: 19596236
J Appl Crystallogr. 2011 Dec 1;44(Pt 6):1285-1287
pubmed: 22477786
Cell. 1994 Dec 2;79(5):853-64
pubmed: 8001122
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Nat Rev Mol Cell Biol. 2001 Jun;2(6):433-43
pubmed: 11389467
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Nucleic Acids Res. 2021 Jul 21;49(13):7740-7752
pubmed: 34181713
Genes Dev. 2010 Jul 15;24(14):1559-69
pubmed: 20634321
Structure. 2022 May 5;30(5):743-752.e3
pubmed: 35290797
Nucleic Acids Res. 2013 Jan 7;41(1):648-56
pubmed: 23118486
Nature. 2022 Sep;609(7927):630-639
pubmed: 36002576
Nat Chem Biol. 2019 Dec;15(12):1241-1248
pubmed: 31611704
Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22
pubmed: 18156677
J Biol Chem. 2002 Feb 22;277(8):5711-4
pubmed: 11756402
Biochemistry. 2000 Dec 26;39(51):16125-34
pubmed: 11123941
Nucleic Acids Res. 2015 Dec 15;43(22):10882-92
pubmed: 26578604
Science. 2017 May 12;356(6338):631-634
pubmed: 28495749
EMBO J. 1992 Feb;11(2):699-704
pubmed: 1537343
Biochem Soc Trans. 2009 Jun;37(Pt 3):519-26
pubmed: 19442245