Abstract
Although PTIP is implicated in the DNA damage response, through interactions with 53BP1, the function of PTIP in the DNA damage response remain elusive. Here, we show that RNF8 controls DNA damage-induced nuclear foci formation of PTIP, which in turn regulates 53BP1 localization to the DNA damage sites. In addition, SMC1, a substrate of ATM, could not be phosphorylated at the DNA damage sites in the absence of PTIP. The PTIP-dependent pathway is important for DNA double strand breaks repair and DNA damage-induced intra-S phase checkpoint activation. Taken together, these results suggest that the role of PTIP in the DNA damage response is downstream of RNF8 and upstream of 53BP1. Thus, PTIP regulates 53BP1-dependent signaling pathway following DNA damage.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antibodies / pharmacology
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Ataxia Telangiectasia Mutated Proteins
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Chromatin / metabolism
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism*
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DNA Breaks, Double-Stranded
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DNA Damage / physiology*
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DNA Repair / physiology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Histones / genetics
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism*
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Osteosarcoma
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Phosphorylation / physiology
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Protein Serine-Threonine Kinases / metabolism
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Rabbits
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Signal Transduction / physiology
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Trans-Activators / genetics
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Tumor Suppressor Proteins / metabolism
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Tumor Suppressor p53-Binding Protein 1
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Ubiquitin-Protein Ligases
Substances
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Adaptor Proteins, Signal Transducing
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Antibodies
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Carrier Proteins
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Cell Cycle Proteins
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Chromatin
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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H2AX protein, human
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Histones
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Intracellular Signaling Peptides and Proteins
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MDC1 protein, human
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Nuclear Proteins
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PAXIP1 protein, human
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RNF8 protein, human
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TP53BP1 protein, human
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Trans-Activators
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Tumor Suppressor Proteins
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Tumor Suppressor p53-Binding Protein 1
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structural maintenance of chromosome protein 1
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Ubiquitin-Protein Ligases
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases