A Meier-Gorlin syndrome mutation impairs the loading of the MCM2-7 complex during DNA replication initiation - PubMed
9 hours ago
- #helicase
- #DNA replication
- #Meier-Gorlin syndrome
- Meier-Gorlin syndrome mutation affects MCM2-7 complex loading during DNA replication initiation.
- MCM2-7 forms a single hexamer (SH) with an open DNA entry gate, and two SHs can form a double hexamer (DH) encircling DNA.
- Cryo-EM shows human MCM2-7 can exist as DH without DNA, with MCM3 winged helix domain (WHD) acting as a safety latch.
- ORC-CDC6 binding opens the safety latch; mutations disrupting this latch cause replication defects and DNA damage.
- Shortening the MCM3 linker alleviates cell cycle defects from latch-strengthening mutations, revealing a regulated MCM2-7 loading step.