Figure 8.

Proposed model for XPA binding at stalled replication forks as a result of PCNA sequestration by progerin. Under normal conditions in the cell the RFC complex loads the replication clamp, PCNA, onto the DNA to progress replication/synthesis. Normally, nuclear XPA is spread throughout the nucleus for activation in the event of a DNA damage. However, as HGPS cells age in culture, progerin accumulates and sequesters PCNA from the replication fork, allowing for XPA binding and inhibiting DNA replication and DNA repair. Ultimately, this process results in genomic instability in these cells.