Mechanism of DNA unwinding by MCM8-9 in complex with HROB
Informazioni aggiuntive
Autori
Acharya A.,
Bret H.,
Huang J. W.,
Martin M.,
Göse M.,
Kissling V. M.,
Ralf S.,
Ciccia A.,
Guérois R.,
Cejka P.
Tipo
Articolo pubblicato in rivista scientifica
Anno
2024
Lingua
Inglese
Sommario
HROB promotes the MCM8-9 helicase in DNA damage response. To understand how HROB activates MCM8-9, we defined their interaction interface. We showed that HROB makes important yet transient contacts with both MCM8 and MCM9, and binds the MCM8-9 heterodimer with the highest affinity. MCM8-9-HROB prefer branched DNA structures, and display low DNA unwinding processivity. MCM8-9 unwinds DNA as a hexamer that assembles from dimers on DNA in the presence of ATP. The hexamer involves two repeating protein-protein interfaces between the alternating MCM8 and MCM9 subunits. One of these interfaces is quite stable and forms an obligate heterodimer across which HROB binds. The other interface is labile and mediates hexamer assembly, independently of HROB. The ATPase site formed at the labile interface contributes disproportionally more to DNA unwinding than that at the stable interface. Here, we show that HROB promotes DNA unwinding downstream of MCM8-9 loading and ring formation on ssDNA.
Parole chiave
DNA, Enzyme mechanisms
Periodico
Nature communications
Volume
15
Pagine (o numero dell’articolo)
3584
Diffusione
Licenza
CC BY
Visibilità
Pubblico
Status open access
Gold
