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Biophys Chem. 2016 Nov 10. pii: S0301-4622(16)30346-5. doi: 10.1016/j.bpc.2016.11.001. [Epub ahead of print]

DNA replication and inter-strand crosslink repair: Symmetric activation of dimeric nanomachines?

Author information

  • 1Macromolecular Machines Laboratory, Clare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms, EN6 3LD, UK.
  • 2Macromolecular Machines Laboratory, Clare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms, EN6 3LD, UK. Electronic address: alessandro.costa@crick.ac.uk.

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.

PMID:
27989548
DOI:
10.1016/j.bpc.2016.11.001
[PubMed - as supplied by publisher]
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