It has been shown that flap endonuclease-1 (FEN-1), a structure-specific nu
clease, acts on the removal of RNA primers during Okazaki fragment maturati
on in DNA synthesis. To study whether the gene expression of FEN-1 is induc
ible during cell proliferation, we analyzed the FEN-1 mRNA levels in active
ly growing cells and non-growing cells. The gene expression of FEN-1 was hi
gher in mitotic cells than in resting cells, and was markedly decreased, es
pecially, when terminal differentiation was induced in promyelocytic leukem
ia cells (HL-60 cells). The decline correlated substantially with the ceasi
ng of DNA synthesis. In the examination of tissue-specific gene expression,
the human testis, spleen, thymus and mucosal lining of colon tissues expre
ssed this gene actively, whereas the prostate, ovary, small intestine and p
eripheral blood leukocyte hardly expressed it. In addition, FEN-1 was co-lo
calized with the proliferating cell nuclear antigen (PCNA) in young rat kid
ney according to immunohistochemistry. These findings suggest that FEN-1 ge
ne expression is inducible during cell proliferation for DNA synthesis, and
is down-regulated during cell differentiation. (C) 2000 Elsevier Science B
.V. All rights reserved.