Mutator specificity and disease: looking over the FENce
Article Abstract:
The discovery of a yeast mutator strain with a unique mutagenic specificity opens new avenues in the search for mutations which drastically increase the rate of mutations in humans, thereby causing cancer and other diseases. The strain has a null mutation in the yeast RAD27(RTH1) gene, a member of a gene family which includes the gene encoding human flap endonuclease, FEN1. There are two potential sequence arrangements besides microsatellites where alterations might be diagnostic of fen1 (rad27) or other mutations different from MMR mutators in human tumors. One is minisatellites and the other is duplications and/or deletions between direct repeats separated by random DNA.
Publication Name: Cell
Subject: Biological sciences
ISSN: 0092-8674
Year: 1997
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Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis
Article Abstract:
Yeast and human cDNA expression libraries for proteins that interact with mismatch repair proteins are screened using a lexA-based two-hybrid system. Both libraries identified an interaction between Mutl proteins and proliferating cell nuclear antigen (PCNA), which was also shown to interact with yeast MSH2. Results indicate that DNA synthesis associated with mismatch repair precedes PCNA's role in the latter process.
Publication Name: Cell
Subject: Biological sciences
ISSN: 0092-8674
Year: 1996
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Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase
Article Abstract:
The mutations result from strand slippage, which in repetitive sequences generates misaligend intermediates stabilized by correct base pairing that support polymerization. It is reported that crystal structures of human DNA polymerase, which frequently generates deletion mutations are bound to such intermediates and each contains an extra helical template nucleotide upstream of the active site.
Publication Name: Cell
Subject: Biological sciences
ISSN: 0092-8674
Year: 2006
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