The molecular machines that replicate the genome consist of many interacting
components. Essential to the organization of the replication machinery are ring-shaped
proteins, like the prokaryotic β-clamp or eukaryotic PCNA (Proliferating Cell Nuclear
Antigen), collectively named sliding clamps. They encircle the DNA molecule and slide on
it freely and bidirectionally. Sliding clamps are typically associated to DNA polymerases
and provide these enzymes with the processivity required to synthesize large chromosomes.
Additionally, they interact with a large array of proteins that perform enzymatic reactions
on DNA, targeting and orchestrating their functions. In recent years there have been a large
number of studies that have analyzed the structural details of how sliding clamps interact
with their ligands. However, much remains to be learned in relation to how these
interactions are regulated to occur coordinately and sequentially. Since sliding clamps
participate in reactions in which many different enzymes bind and then release from the
clamp in an orchestrated way, it is critical to analyze how these changes in affinity take
place. In this review I focus the attention on the mechanisms by which various types of
enzymes interact with sliding clamps and what is known about the regulation of this
binding. Especially I describe emerging paradigms on how enzymes switch places on
sliding clamps during DNA replication and repair of prokaryotic and eukaryotic genomes.
Keywords: DNA replication, DNA repair, PCNA, beta clamp, DNA polymerase,
MutS.