Abstract
Bloom syndrome is a disorder of profound and early cancer predisposition in which cells become hypermutable, exhibit high frequency of sister chromatid exchanges, and show increased micronuclei. BLM, the gene mutated in Bloom syndrome, has been cloned previously, and the BLM protein is a member of the RecQ family of DNA helicases. Many lines of evidence suggest that BLM is involved either directly in DNA replication or in surveillance during DNA replication, but its specific roles remain unknown. Here we show that hBLM can suppress both the temperature-sensitive growth defect and the DNA damage sensitivity of the yeast DNA replication mutant dna2-1. The dna2-1 mutant is defective in a helicase-nuclease that is required either to coordinate with the crucial Saccharomyces cerevisiae (sc) FEN1 nuclease in Okazaki fragment maturation or to compensate for scFEN1 when its activity is impaired. We show that human BLM interacts with both scDna2 and scFEN1 by using coimmunoprecipitation from yeast extracts, suggesting that human BLM participates in the same steps of DNA replication or repair as scFEN1 and scDna2.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphatases / deficiency
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / physiology*
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Alkylating Agents / pharmacology
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Bloom Syndrome / enzymology*
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Bloom Syndrome / genetics
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DNA Helicases / deficiency
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DNA Helicases / genetics
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DNA Helicases / physiology*
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DNA Repair / genetics
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DNA Repair / physiology*
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DNA Replication / genetics
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DNA Replication / physiology
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DNA, Fungal / drug effects
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DNA, Fungal / genetics
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DNA, Fungal / metabolism
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Enzyme Inhibitors / pharmacology
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Exodeoxyribonuclease V
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Exodeoxyribonucleases / deficiency
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Exodeoxyribonucleases / genetics
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Exodeoxyribonucleases / physiology*
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Genetic Complementation Test
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Humans
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Hydroxyurea / pharmacology
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Methyl Methanesulfonate / pharmacology
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Protein Interaction Mapping
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RecQ Helicases
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Ribonucleotide Reductases / antagonists & inhibitors
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / physiology*
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Saccharomyces cerevisiae Proteins / antagonists & inhibitors
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / physiology*
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Temperature
Substances
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Alkylating Agents
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DNA, Fungal
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Enzyme Inhibitors
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Saccharomyces cerevisiae Proteins
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Methyl Methanesulfonate
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Ribonucleotide Reductases
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Exodeoxyribonucleases
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Exodeoxyribonuclease V
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Adenosine Triphosphatases
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Bloom syndrome protein
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DNA Helicases
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DNA2 protein, S cerevisiae
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RecQ Helicases
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Hydroxyurea