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Yan H , Chen CY , Kobayashi R , Newport J
Replication focus-forming activity 1 and the Werner syndrome gene product
Nature Genetics. 1998 Aug;19(4) :375-378
AbstractThe 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 binds single-stranded DNA that stabilizes the unwound origin(1). In eukaryotic cells, the origin recognition complex(2) (ORC) is the initiator protein 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 Saccharomyces cerevisiae. A unique feature of eukaryotic DNA replication is that it occurs at a few-hundred discrete foci(4). It has thus been proposed that a real origin must contain a specific DNA sequence and must be 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 associated with premature ageing in humans(6).
NotesTimes Cited: 76 English Article 106AM NAT GENET