title: DNA replication and inter-strand crosslink repair: Symmetric activation of dimeric nanomachines?
abstract: Eukaryotic DNA replication initiation and the Fanconi anemia pathway of interstrand crosslink repair both revolve around the recruitment of a set of DNA-processing factors onto a dimeric protein complex, which functions as a loading platform (MCM and FANCI-FANCD2 respectively). Here we compare and contrast the two systems, identifying a set of unresolved mechanistic questions. How is the dimeric loading platform assembled on the DNA? How can equivalent covalent modification of both factors in a dimer be achieved? Are multicomponent DNA-interacting machines built symmetrically around their dimeric loading platform? Recent biochemical reconstitution studies are starting to shed light on these issues.
authors.affiliation: Macromolecular Machines Laboratory, Clare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms, EN6 3LD, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Swuec
authors.affiliation: Macromolecular Machines Laboratory, Clare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms, EN6 3LD, UK. Electronic address: alessandro.costa@crick.ac.uk.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Costa
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry; D004260:DNA Repair; D004261:DNA Replication; D019281:Dimerization; D005199:Fanconi Anemia; D052236:Fanconi Anemia Complementation Group D2 Protein; D006801:Humans
chemical_list: D052236:Fanconi Anemia Complementation Group D2 Protein; D004247:DNA