Abstract
The Rb protein suppresses development of an abnormal state of endoreduplication arising after S phase DNA damage. In diploid, S phase cells, the activity of protein phosphatase 2A (PP2A) licenses the stable association of un(der)phosphorylated Rb with chromatin. After damage, chromatin-associated pRb is attracted to certain chromosomal replication initiation sites in the order in which they normally fire. Like S phase DNA damage in Rb(-/-) cells, specific interruption of PP2A function in irradiated, S phase wt cells also elicited a state of endoreduplication. Thus, PP2A normally licenses the recruitment of Rb to chromatin sites in S phase from which, after DNA damage, it relocalizes to selected replication control sites and suppresses abnormal, postdamage rereplicative activity.
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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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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Cell Nucleus / radiation effects
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Cells, Cultured
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Chromatin / genetics
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Chromatin / metabolism*
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Chromatin / radiation effects
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DNA Damage*
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DNA Replication / genetics*
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DNA Replication / radiation effects
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Fibroblasts / metabolism
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Fibroblasts / radiation effects
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Humans
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Mutation / genetics
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism
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Phosphoprotein Phosphatases / radiation effects
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Protein Phosphatase 2
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism*
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Retinoblastoma Protein / radiation effects
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S Phase / genetics*
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S Phase / radiation effects
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T-Lymphocytes / metabolism
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T-Lymphocytes / radiation effects
Substances
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Chromatin
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Retinoblastoma Protein
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Phosphoprotein Phosphatases
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Protein Phosphatase 2