Abstract
Mre11, Rad50, and Nbs1 form a conserved heterotrimeric complex that is involved in recombination and DNA damage checkpoints. Mutations in this complex disrupt the S-phase DNA damage checkpoint, the checkpoint which slows replication in response to DNA damage, and cause chromosome instability and cancer in humans. However, how these proteins function and specifically where they act in the checkpoint signaling pathway remain crucial questions. We identified fission yeast Nbs1 by using a comparative genomic approach and showed that the genes for human Nbs1 and fission yeast Nbs1 and that for their budding yeast counterpart, Xrs2, are members of an evolutionarily related but rapidly diverging gene family. Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint. Our results suggest that a complex of Rad32, Rad50, and Nbs1 acts specifically in the S-phase branch of the DNA damage checkpoint and is not involved in general DNA damage recognition or signaling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Cell Cycle Proteins / genetics
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Chromosomal Proteins, Non-Histone / genetics*
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Chromosomal Proteins, Non-Histone / metabolism*
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Cloning, Molecular
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Conserved Sequence
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DNA Damage / physiology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Endodeoxyribonucleases / genetics
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Endodeoxyribonucleases / metabolism
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Evolution, Molecular
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Exodeoxyribonucleases / genetics
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Exodeoxyribonucleases / metabolism
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G2 Phase / genetics
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Gene Expression Regulation, Fungal
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Macromolecular Substances
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Methyl Methanesulfonate / pharmacology
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Molecular Sequence Data
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Nuclear Proteins / genetics
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S Phase / genetics*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Schizosaccharomyces / cytology
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Schizosaccharomyces / drug effects
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Schizosaccharomyces / genetics*
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Schizosaccharomyces pombe Proteins / genetics*
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Schizosaccharomyces pombe Proteins / metabolism*
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Sequence Homology, Amino Acid
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Telomere / genetics
Substances
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Macromolecular Substances
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NBN protein, human
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Nbs1 protein, S pombe
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Nuclear Proteins
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RAD50 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Schizosaccharomyces pombe Proteins
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XRS2 protein, S cerevisiae
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Methyl Methanesulfonate
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Endodeoxyribonucleases
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Exodeoxyribonucleases
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MRE11 protein, S cerevisiae
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Mre11 protein, S pombe