Replication focus-forming activity 1 and the Werner syndrome gene product

Nat Genet. 1998 Aug;19(4):375-8. doi: 10.1038/1263.

Abstract

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 binds single-stranded DNA that stabilizes the unwound origin. In eukaryotic cells, the origin recognition complex (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. 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. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • DNA / metabolism
  • DNA Helicases / genetics*
  • DNA Helicases / isolation & purification
  • DNA Helicases / metabolism*
  • DNA Replication / physiology*
  • DNA-Binding Proteins / metabolism
  • Exodeoxyribonucleases
  • Humans
  • Molecular Sequence Data
  • RecQ Helicases
  • Replication Protein A
  • Sequence Homology, Amino Acid
  • Werner Syndrome / genetics
  • Werner Syndrome Helicase
  • Xenopus laevis

Substances

  • DNA-Binding Proteins
  • RPA1 protein, human
  • Replication Protein A
  • Adenosine Triphosphate
  • DNA
  • Exodeoxyribonucleases
  • DNA Helicases
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase

Associated data

  • GENBANK/AF067418