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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
DNA replication and inter-strand crosslink repair: Symmetric activation of dimeric nanomachines?
Paolo Swuec1, Alessandro Costa1
1Macromolecular Machines Laboratory, Clare Hall Laboratory, The Francis Crick Institute, Blanche Lane, South Mimms, EN6 3LD, 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.
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