Nuclear pore complexes mediate subtelomeric gene silencing by regulating PCNA levels on chromatin

The nuclear pore complex (NPC) physically interacts with chromatin and regulates gene expression. The Saccharomyces cerevisiae inner ring nucleoporin Nup170 has been implicated in chromatin organization and the maintenance of gene silencing in subtelomeric regions. To gain insight into how Nup170 regulates this process, we used protein-protein interactions, genetic interactions, and transcriptome correlation analyses to identify the Ctf18-RFC complex, an alternative proliferating cell nuclear antigen (PCNA) loader, as a facilitator of the gene regulatory functions of Nup170. The Ctf18-RFC complex is recruited to a subpopulation of NPCs that lack the nuclear basket proteins Mlp1 and Mlp2. In the absence of Nup170, PCNA levels on DNA are reduced, resulting in the loss of silencing of subtelomeric genes. Increasing PCNA levels on DNA by removing Elg1, which is required for PCNA unloading, rescues subtelomeric silencing defects in nup170 & UDelta;. The NPC, therefore, mediates subtelomeric gene silencing by regulating PCNA levels on DNA. Kumar et al. report that the yeast nucleoporin Nup170 regulates chromatin silencing through the Ctf18-RFC, an alternative PCNA loader, to establish PCNA levels on DNA in a cell cycle-regulated manner. Increasing PCNA levels by removing Elg1 restores silencing defects. They ascribe this chromatin silencing function to a subset of NPCs.