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Vertebrate cells lacking FEN-1 endonuclease are viable but hypersensitive to methylating agents and H2O2.

ABSTRACT: The structure-specific FEN-1 endonuclease has been implicated in various cellular processes, including DNA replication, repair and recombination. In vertebrate cells, however, no in vivo evidence has been provided so far. Here, we knocked out the FEN-1 gene (FEN1) in the chicken DT40 cell line. Surprisingly, homozygous mutant (FEN1-/-) cells were viable, indicating that FEN-1 is not essential for cell proliferation and thus for Okazaki fragment processing during DNA replication. However, compared with wild-type cells, FEN1-/- cells exhibited a slow growth phenotype, probably due to a high rate of cell death. The mutant cells were hypersensitive to methylmethane sulfonate, N-methyl-N'-nitro-N-nitrosoguanidine and H2O2, but not to UV light, X-rays and etoposide, suggesting that FEN-1 functions in base excision repair in vertebrate cells.

SUBMITTER: Matsuzaki Y

PROVIDER: S-EPMC135760 | biostudies-literature | 2002 Jul

REPOSITORIES: biostudies-literature

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Vertebrate cells lacking FEN-1 endonuclease are viable but hypersensitive to methylating agents and H2O2.

Matsuzaki Yasuo Y Adachi Noritaka N Koyama Hideki H

Nucleic acids research 20020701 14

The structure-specific FEN-1 endonuclease has been implicated in various cellular processes, including DNA replication, repair and recombination. In vertebrate cells, however, no in vivo evidence has been provided so far. Here, we knocked out the FEN-1 gene (FEN1) in the chicken DT40 cell line. Surprisingly, homozygous mutant (FEN1-/-) cells were viable, indicating that FEN-1 is not essential for cell proliferation and thus for Okazaki fragment processing during DNA replication. However, compare ...[more]

PMID: 12136109

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