Nucleic Acids Research, Vol 24, Issue 11 2036-2043, Copyright © 1996 by Oxford University Press
X Wu, J Li, X Li, CL Hsieh, PM Burgers and MR Lieber
In eukaryotic cells, a 5' flap DNA endonuclease activity and a ds DNA
5'-exonuclease activity exist within a single enzyme called FEN-1 [flap
endo-nuclease and 5(five)'-exo-nuclease]. This 42 kDa endo- /exonuclease,
FEN-1, is highly homologous to human XP-G, Saccharomyces cerevisiae RAD2
and S.cerevisiae RTH1. These structure-specific nucleases recognize and
cleave a branched DNA structure called a DNA flap, and its derivative
called a pseudo Y-structure. FEN-1 is essential for lagging strand DNA
synthesis in Okazaki fragment joining. FEN-1 also appears to be important
in mismatch repair. Here we find that human PCNA, the processivity factor
for eukaryotic polymerases, physically associates with human FEN-1 and
stimulates its endonucleolytic activity at branched DNA structures and its
exonucleolytic activity at nick and gap structures. Structural requirements
for FEN-1 and PCNA loading provide an interesting picture of this
stimulation. PCNA loads on to substrates at double-stranded DNA ends. In
contrast, FEN-1 requires a free single-stranded 5' terminus and appears to
load by tracking along the single-stranded DNA branch. These physical
constraints define the range of DNA replication, recombination and repair
processes in which this family of structure- specific nucleases
participate. A model explaining the exonucleolytic activity of FEN-1 in
terms of its endonucleolytic activity is proposed based on these
observations.
ARTICLES
Processing of branched DNA intermediates by a complex of human FEN-1 and PCNA
Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA.
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