Abstract
53BP1 binds to the tumor suppressor protein p53 and has a potential role in DNA damage responses. We used small interfering RNA (siRNA) directed against 53BP1 in mammalian cells to demonstrate that 53BP1 is a key transducer of the DNA damage checkpoint signal. 53BP1 was required for p53 accumulation, G2-M checkpoint arrest, and the intra-S-phase checkpoint in response to ionizing radiation. 53BP1 played a partially redundant role in phosphorylation of the downstream checkpoint effector proteins Brca1 and Chk2 but was required for the formation of Brca1 foci in a hierarchical branched pathway for the recruitment of repair and signaling proteins to sites of DNA damage.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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BRCA1 Protein / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / metabolism
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Checkpoint Kinase 2
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DNA / biosynthesis
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DNA Damage*
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G2 Phase*
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Histones / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins*
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Mitosis*
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Nuclear Proteins / metabolism
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Phosphoproteins*
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Phosphorylation
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases*
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RNA, Small Interfering
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Radiation, Ionizing
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S Phase*
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Signal Transduction
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor p53-Binding Protein 1
Substances
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BRCA1 Protein
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Carrier Proteins
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Cell Cycle Proteins
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Histones
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Intracellular Signaling Peptides and Proteins
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NBN protein, human
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Nuclear Proteins
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Phosphoproteins
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RNA, Small Interfering
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TP53BP1 protein, human
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Tumor Suppressor Protein p53
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Tumor Suppressor p53-Binding Protein 1
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DNA
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Protein Kinases
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Checkpoint Kinase 2
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CHEK2 protein, human
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Protein Serine-Threonine Kinases