wEukaryotic cells must be able to coordinate DNA repair, replication and cell cycle progression in response to DNA damage. A failure to activate the checkpoints which delay the cell cycle in response to internal and external cues and to repair the DNA lesions results in an increase in genetic instability and cancer predisposition, The use of the yeast Saccharomyces cerevisiae has been invaluable in isolating many of the genes required for the DNA damage response, although the molecular mechanisms which couple this regulatory pathway to different DNA transactions are still largely unknown. In analogy with prokaryotes, we propose that DNA strand breaks, caused by genotoxic agents or by replication-related lesions, trigger a replication coupled repair mechanism, dependent upon recombination, which is induced by the checkpoint acting during S-phase.
机构:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA
机构:
Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA
Beth Israel Deaconess Med Ctr, Canc Res Inst, Boston, MA 02215 USA
Harvard Med Sch, Boston, MA 02215 USAUniv Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
Willis, Nicholas A.
Zhou, Chunshui
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Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Dept Genet, Boston, MA 02115 USA
Harbin Med Univ, Med Genet Lab, Harbin 150081, Peoples R ChinaUniv Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
Zhou, Chunshui
Elia, Andrew E. H.
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Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Dept Genet, Boston, MA 02115 USA
Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USAUniv Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
Elia, Andrew E. H.
Murray, Johanne M.
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Univ Sussex, Sch Life Sci, Genome Damage & Stabil Ctr, Falmer BN1 9RQ, E Sussex, EnglandUniv Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
Murray, Johanne M.
Carr, Antony M.
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Univ Sussex, Sch Life Sci, Genome Damage & Stabil Ctr, Falmer BN1 9RQ, E Sussex, EnglandUniv Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
Carr, Antony M.
Elledge, Stephen J.
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Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Dept Genet, Boston, MA 02115 USA
Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USAUniv Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
Elledge, Stephen J.
Rhind, Nicholas
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Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USAUniv Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA