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A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation
by
Boonen, Rick A
, Typas, Dimitris
, Wiegant, Wouter W
, van Attikum, Haico
, Heuvel, Diana van den
, Couturier, Anthony M
, Mullenders, Leon H
, Masson, Jean-Yves
, Luijsterburg, Martijn S
, Caron, Marie-Christine
in
Animals
/ Biochemistry
/ Breast cancer
/ Cell Biology
/ Cell cycle
/ Cell Cycle - genetics
/ Cell Cycle - radiation effects
/ Cell Line, Transformed
/ Cell Line, Tumor
/ Chromatin
/ Deoxyribonucleic acid
/ DNA
/ DNA - genetics
/ DNA - metabolism
/ DNA Breaks, Double-Stranded - radiation effects
/ DNA damage
/ DNA repair
/ Double-strand break repair
/ Fanconi Anemia Complementation Group N Protein - genetics
/ Fanconi Anemia Complementation Group N Protein - metabolism
/ Fibroblasts - cytology
/ Fibroblasts - metabolism
/ Fibroblasts - radiation effects
/ Genetic recombination
/ Genomes
/ Glycerol
/ HEK293 Cells
/ Histone H2A
/ Histones - genetics
/ Histones - metabolism
/ Homologous recombination
/ Humans
/ Lasers, Excimer
/ Medical research
/ Mice
/ Mouse Embryonic Stem Cells - cytology
/ Mouse Embryonic Stem Cells - metabolism
/ Mouse Embryonic Stem Cells - radiation effects
/ Observations
/ Osteoblasts - cytology
/ Osteoblasts - metabolism
/ Osteoblasts - radiation effects
/ PALB2
/ Physiological aspects
/ Protein Binding
/ Protein Interaction Domains and Motifs
/ Proteins
/ Recombinational DNA Repair
/ RNF168
/ Telomere-Binding Proteins - genetics
/ Telomere-Binding Proteins - metabolism
/ Ubiquitin
/ Ubiquitin - genetics
/ Ubiquitin - metabolism
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ Ubiquitination
/ ubiquitylation
/ X-Rays
2017
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A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation
by
Boonen, Rick A
, Typas, Dimitris
, Wiegant, Wouter W
, van Attikum, Haico
, Heuvel, Diana van den
, Couturier, Anthony M
, Mullenders, Leon H
, Masson, Jean-Yves
, Luijsterburg, Martijn S
, Caron, Marie-Christine
in
Animals
/ Biochemistry
/ Breast cancer
/ Cell Biology
/ Cell cycle
/ Cell Cycle - genetics
/ Cell Cycle - radiation effects
/ Cell Line, Transformed
/ Cell Line, Tumor
/ Chromatin
/ Deoxyribonucleic acid
/ DNA
/ DNA - genetics
/ DNA - metabolism
/ DNA Breaks, Double-Stranded - radiation effects
/ DNA damage
/ DNA repair
/ Double-strand break repair
/ Fanconi Anemia Complementation Group N Protein - genetics
/ Fanconi Anemia Complementation Group N Protein - metabolism
/ Fibroblasts - cytology
/ Fibroblasts - metabolism
/ Fibroblasts - radiation effects
/ Genetic recombination
/ Genomes
/ Glycerol
/ HEK293 Cells
/ Histone H2A
/ Histones - genetics
/ Histones - metabolism
/ Homologous recombination
/ Humans
/ Lasers, Excimer
/ Medical research
/ Mice
/ Mouse Embryonic Stem Cells - cytology
/ Mouse Embryonic Stem Cells - metabolism
/ Mouse Embryonic Stem Cells - radiation effects
/ Observations
/ Osteoblasts - cytology
/ Osteoblasts - metabolism
/ Osteoblasts - radiation effects
/ PALB2
/ Physiological aspects
/ Protein Binding
/ Protein Interaction Domains and Motifs
/ Proteins
/ Recombinational DNA Repair
/ RNF168
/ Telomere-Binding Proteins - genetics
/ Telomere-Binding Proteins - metabolism
/ Ubiquitin
/ Ubiquitin - genetics
/ Ubiquitin - metabolism
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ Ubiquitination
/ ubiquitylation
/ X-Rays
2017
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A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation
by
Boonen, Rick A
, Typas, Dimitris
, Wiegant, Wouter W
, van Attikum, Haico
, Heuvel, Diana van den
, Couturier, Anthony M
, Mullenders, Leon H
, Masson, Jean-Yves
, Luijsterburg, Martijn S
, Caron, Marie-Christine
in
Animals
/ Biochemistry
/ Breast cancer
/ Cell Biology
/ Cell cycle
/ Cell Cycle - genetics
/ Cell Cycle - radiation effects
/ Cell Line, Transformed
/ Cell Line, Tumor
/ Chromatin
/ Deoxyribonucleic acid
/ DNA
/ DNA - genetics
/ DNA - metabolism
/ DNA Breaks, Double-Stranded - radiation effects
/ DNA damage
/ DNA repair
/ Double-strand break repair
/ Fanconi Anemia Complementation Group N Protein - genetics
/ Fanconi Anemia Complementation Group N Protein - metabolism
/ Fibroblasts - cytology
/ Fibroblasts - metabolism
/ Fibroblasts - radiation effects
/ Genetic recombination
/ Genomes
/ Glycerol
/ HEK293 Cells
/ Histone H2A
/ Histones - genetics
/ Histones - metabolism
/ Homologous recombination
/ Humans
/ Lasers, Excimer
/ Medical research
/ Mice
/ Mouse Embryonic Stem Cells - cytology
/ Mouse Embryonic Stem Cells - metabolism
/ Mouse Embryonic Stem Cells - radiation effects
/ Observations
/ Osteoblasts - cytology
/ Osteoblasts - metabolism
/ Osteoblasts - radiation effects
/ PALB2
/ Physiological aspects
/ Protein Binding
/ Protein Interaction Domains and Motifs
/ Proteins
/ Recombinational DNA Repair
/ RNF168
/ Telomere-Binding Proteins - genetics
/ Telomere-Binding Proteins - metabolism
/ Ubiquitin
/ Ubiquitin - genetics
/ Ubiquitin - metabolism
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ Ubiquitination
/ ubiquitylation
/ X-Rays
2017
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A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation
Journal Article
A PALB2-interacting domain in RNF168 couples homologous recombination to DNA break-induced chromatin ubiquitylation
2017
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Overview
DNA double-strand breaks (DSB) elicit a ubiquitylation cascade that controls DNA repair pathway choice. This cascade involves the ubiquitylation of histone H2A by the RNF168 ligase and the subsequent recruitment of RIF1, which suppresses homologous recombination (HR) in G1 cells. The RIF1-dependent suppression is relieved in S/G2 cells, allowing PALB2-driven HR to occur. With the inhibitory impact of RIF1 relieved, it remains unclear how RNF168-induced ubiquitylation influences HR. Here, we uncover that RNF168 links the HR machinery to H2A ubiquitylation in S/G2 cells. We show that PALB2 indirectly recognizes histone ubiquitylation by physically associating with ubiquitin-bound RNF168. This direct interaction is mediated by the newly identified PALB2-interacting domain (PID) in RNF168 and the WD40 domain in PALB2, and drives DNA repair by facilitating the assembly of PALB2-containing HR complexes at DSBs. Our findings demonstrate that RNF168 couples PALB2-dependent HR to H2A ubiquitylation to promote DNA repair and preserve genome integrity.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ Cell Cycle - radiation effects
/ DNA
/ DNA Breaks, Double-Stranded - radiation effects
/ Fanconi Anemia Complementation Group N Protein - genetics
/ Fanconi Anemia Complementation Group N Protein - metabolism
/ Fibroblasts - radiation effects
/ Genomes
/ Glycerol
/ Humans
/ Mice
/ Mouse Embryonic Stem Cells - cytology
/ Mouse Embryonic Stem Cells - metabolism
/ Mouse Embryonic Stem Cells - radiation effects
/ Osteoblasts - radiation effects
/ PALB2
/ Protein Interaction Domains and Motifs
/ Proteins
/ RNF168
/ Telomere-Binding Proteins - genetics
/ Telomere-Binding Proteins - metabolism
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ X-Rays
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