MCM ring hexamerization is a prerequisite for DNA-binding

Froelich, Clifford A.; Nourse, Amanda; Enemark, Eric J.

doi:10.1093/nar/gkv914

Title: MCM ring hexamerization is a prerequisite for DNA-binding

Journal Article · Sun Sep 13 00:00:00 EDT 2015 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkv914· OSTI ID:1223715

Froelich, Clifford A. ^[1]; Nourse, Amanda ^[1]; Enemark, Eric J. ^[1]

St. Jude Children's Research Hospital, Memphis, TN (United States)

The hexameric Minichromosome Maintenance (MCM) protein complex forms a ring that unwinds DNA at the replication fork in eukaryotes and archaea. Our recent crystal structure of an archaeal MCM N-terminal domain bound to single-stranded DNA (ssDNA) revealed ssDNA associating across tight subunit interfaces but not at the loose interfaces, indicating that DNA-binding is governed not only by the DNA-binding residues of the subunits (MCM ssDNA-binding motif, MSSB) but also by the relative orientation of the subunits. We now extend these findings to show that DNA-binding by the MCM N-terminal domain of the archaeal organism Pyrococcus furiosus occurs specifically in the hexameric oligomeric form. We show that mutants defective for hexamerization are defective in binding ssDNA despite retaining all the residues observed to interact with ssDNA in the crystal structure. One mutation that exhibits severely defective hexamerization and ssDNA-binding is at a conserved phenylalanine that aligns with the mouse Mcm4(Chaos3) mutation associated with chromosomal instability, cancer, and decreased intersubunit association.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357; W-31-109-ENG-38

OSTI ID:: 1223715

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 6 works

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