Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder because 
of a LMNA gene mutation that produces a mutant lamin A protein (progerin). 
Progerin also has been correlated to physiological aging and related diseases. 
However, how progerin causes the progeria remains unknown. Here, we report that 
the large subunit (RFC1) of replication factor C is cleaved in HGPS cells, 
leading to the production of a truncated RFC1 of ~ 75 kDa, which appears to be 
defective in loading proliferating cell nuclear antigen (PCNA) and pol δ onto 
DNA for replication. Interestingly, the cleavage can be inhibited by a serine 
protease inhibitor, suggesting that RFC1 is cleaved by a serine protease. 
Because of the crucial role of RFC in DNA replication, our findings provide a 
mechanistic interpretation for the observed early replicative arrest and 
premature aging phenotypes of HPGS and may lead to novel strategies in HGPS 
treatment. Furthermore, this unique truncated form of RFC1 may serve as a 
potential marker for HGPS.