REPLICATION FOCUS-FORMING ACTIVITY-1 AND THE WERNER-SYNDROME GENE-PRODUCT

The initiation of DNA replication involves a minimum of four factors: a specific DNA sequence (origin), an initiator protein which binds to the origin, a helicase that unwinds the origin and a protein that bind s single-stranded DNA that stabilizes the unwound origin(1). In eukary otic cells, the origin recognition complex(2) (ORC) is the initiator p rotein and replication protein A (RPA; ref. 3) is the single-stranded DNA-binding protein. However, the helicase has not been identified and the nature of origins remains elusive, except in the case of Saccharo myces cerevisiae. A unique feature of eukaryotic DNA replication is th at it occurs at a few-hundred discrete foci(4). It has thus been propo sed that a real origin must contain a specific DNA sequence and must b e attached to replication foci. Using Xenopus laevis egg extracts, we have identified and purified a 170-kD protein, focus-forming activity 1 (FFA-1), which is required for the formation of replication foci(5). Here we report that FFA-1 has DNA-helicase activity. Moreover, it is a homologue of the human Werner syndrome gene product WRN, a protein a ssociated with premature ageing in humans(6).