Nuclease-deficient FEN-1 blocks Rad51/BRCA1-mediated repair and causes trinucleotide repeat instability.
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ABSTRACT:
SUBMITTER: Spiro C
PROVIDER: S-EPMC180932 | biostudies-literature | 2003 Sep
REPOSITORIES: biostudies-literature
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Nuclease-deficient FEN-1 blocks Rad51/BRCA1-mediated repair and causes trinucleotide repeat instability.
Spiro Craig C McMurray Cynthia T CT
Molecular and cellular biology 20030901 17
Previous studies have shown that expansion-prone repeats form structures that inhibit human flap endonuclease (FEN-1). We report here that faulty processing by FEN-1 initiates repeat instability in mammalian cells. Disease-length CAG tracts in Huntington's disease mice heterozygous for FEN-1 display a tendency toward expansions over contractions during intergenerational inheritance compared to those in homozygous wild-type mice. Further, with regard to human cells expressing a nuclease-defective ...[more]
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