Abstract:
:Flap endonuclease 1 (FEN1) has been shown to remove 5' overhanging flap intermediates during base excision repair and to process the 5' ends of Okazaki fragments during lagging-strand DNA replication in vitro. To assess the in vivo role of the mammalian enzyme in repair and replication, we used a gene-targeting approach to generate mice lacking a functional Fen1 gene. Heterozygote animals appear normal, whereas complete depletion of FEN1 causes early embryonic lethality. Fen1(-/-) blastocysts fail to form inner cell mass during cellular outgrowth, and a complete inactivation of DNA synthesis in giant cells of blastocyst outgrowth was observed. Exposure of Fen1(-/-) blastocysts to gamma radiation caused extensive apoptosis, implying an essential role for FEN1 in the repair of radiation-induced DNA damage in vivo. Our data thus provide in vivo evidence for an essential function of FEN1 in DNA repair, as well as in DNA replication.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Larsen E,Gran C,Saether BE,Seeberg E,Klungland Adoi
10.1128/mcb.23.15.5346-5353.2003subject
Has Abstractpub_date
2003-08-01 00:00:00pages
5346-53issue
15eissn
0270-7306issn
1098-5549journal_volume
23pub_type
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