Elg1, a master guardian of genomic and epigenomic stability

Timely unloading of the DNA polymerase processivity factor PCNA from the replication fork is essential for genome integrity. The conserved yeast Elg1 interacts with the Rfc2-5 subunits of the Replication Factor C (RFC) complex to form an RFC-like complex (RLC). The Elg1-RLC is the principal unloader of chromatin-bound PCNA, and thus plays a central role in DNA replication, DNA recombination and genomic stability maintenance. Mutations in Elg1 lead to hyper-recombination, chromosome loss, longer telomeres, hyper-transposition, chromatin silencing problems and sensitivity to DNA damage agents in yeast, and to death or cancer development in mammals. Thus, Elg1 affects a number of central processes in the cell. In addition, Elg1 is a target of the DNA damage Response (DDR), as well as an amplifier of the DNA damage signal. A novel assay shows that Elg1 plays a role in the establishment and maintenance of heterochromatic regions in the yeast genome. We will discuss possible mechanisms by which Elg1 function links chromatin maintenance and epigenetic memory to DNA replication and DNA repair.