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ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB
by
Tan, Jun
, Shi, Yi
, Teng, Yaqun
, Liang, Zhuobin
, Duan, Meihan
, Gao, Boya
, Lan, Li
, Levine, Arthur S.
, Liu, Yang
, Xiang, Yufei
, Yadav, Tribhuwan
, Zou, Lee
, Nakajima, Satoshi
, Xu, Jianquan
in
101/58
/ 13
/ 13/1
/ 13/51
/ 13/89
/ 147/135
/ 38/109
/ 38/15
/ 38/22
/ 38/23
/ 38/77
/ 42/35
/ 631/337/1427/2122
/ 631/337/149
/ 82/80
/ 82/83
/ Amino Acid Sequence
/ Base Sequence
/ BRCA1 protein
/ BRCA1 Protein - genetics
/ BRCA1 Protein - metabolism
/ BRCA2 protein
/ BRCA2 Protein - genetics
/ BRCA2 Protein - metabolism
/ Breast cancer
/ Cell Line, Tumor
/ Cockayne syndrome
/ Damage localization
/ Deoxyribonucleic acid
/ DNA
/ DNA - genetics
/ DNA - metabolism
/ DNA Damage
/ DNA Helicases - genetics
/ DNA Helicases - metabolism
/ DNA Repair
/ DNA Repair Enzymes - genetics
/ DNA Repair Enzymes - metabolism
/ Genomes
/ HEK293 Cells
/ Homologous Recombination
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Localization
/ multidisciplinary
/ Poly-ADP-Ribose Binding Proteins - genetics
/ Poly-ADP-Ribose Binding Proteins - metabolism
/ Protein B
/ Proteins
/ Rad51 Recombinase - genetics
/ Rad51 Recombinase - metabolism
/ Rad52 DNA Repair and Recombination Protein - genetics
/ Rad52 DNA Repair and Recombination Protein - metabolism
/ Rad52 protein
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Ribonucleic acid
/ RNA
/ Science
/ Science (multidisciplinary)
/ Sequence Homology, Amino Acid
/ Transcription
/ Transcription, Genetic
2018
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ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB
by
Tan, Jun
, Shi, Yi
, Teng, Yaqun
, Liang, Zhuobin
, Duan, Meihan
, Gao, Boya
, Lan, Li
, Levine, Arthur S.
, Liu, Yang
, Xiang, Yufei
, Yadav, Tribhuwan
, Zou, Lee
, Nakajima, Satoshi
, Xu, Jianquan
in
101/58
/ 13
/ 13/1
/ 13/51
/ 13/89
/ 147/135
/ 38/109
/ 38/15
/ 38/22
/ 38/23
/ 38/77
/ 42/35
/ 631/337/1427/2122
/ 631/337/149
/ 82/80
/ 82/83
/ Amino Acid Sequence
/ Base Sequence
/ BRCA1 protein
/ BRCA1 Protein - genetics
/ BRCA1 Protein - metabolism
/ BRCA2 protein
/ BRCA2 Protein - genetics
/ BRCA2 Protein - metabolism
/ Breast cancer
/ Cell Line, Tumor
/ Cockayne syndrome
/ Damage localization
/ Deoxyribonucleic acid
/ DNA
/ DNA - genetics
/ DNA - metabolism
/ DNA Damage
/ DNA Helicases - genetics
/ DNA Helicases - metabolism
/ DNA Repair
/ DNA Repair Enzymes - genetics
/ DNA Repair Enzymes - metabolism
/ Genomes
/ HEK293 Cells
/ Homologous Recombination
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Localization
/ multidisciplinary
/ Poly-ADP-Ribose Binding Proteins - genetics
/ Poly-ADP-Ribose Binding Proteins - metabolism
/ Protein B
/ Proteins
/ Rad51 Recombinase - genetics
/ Rad51 Recombinase - metabolism
/ Rad52 DNA Repair and Recombination Protein - genetics
/ Rad52 DNA Repair and Recombination Protein - metabolism
/ Rad52 protein
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Ribonucleic acid
/ RNA
/ Science
/ Science (multidisciplinary)
/ Sequence Homology, Amino Acid
/ Transcription
/ Transcription, Genetic
2018
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ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB
by
Tan, Jun
, Shi, Yi
, Teng, Yaqun
, Liang, Zhuobin
, Duan, Meihan
, Gao, Boya
, Lan, Li
, Levine, Arthur S.
, Liu, Yang
, Xiang, Yufei
, Yadav, Tribhuwan
, Zou, Lee
, Nakajima, Satoshi
, Xu, Jianquan
in
101/58
/ 13
/ 13/1
/ 13/51
/ 13/89
/ 147/135
/ 38/109
/ 38/15
/ 38/22
/ 38/23
/ 38/77
/ 42/35
/ 631/337/1427/2122
/ 631/337/149
/ 82/80
/ 82/83
/ Amino Acid Sequence
/ Base Sequence
/ BRCA1 protein
/ BRCA1 Protein - genetics
/ BRCA1 Protein - metabolism
/ BRCA2 protein
/ BRCA2 Protein - genetics
/ BRCA2 Protein - metabolism
/ Breast cancer
/ Cell Line, Tumor
/ Cockayne syndrome
/ Damage localization
/ Deoxyribonucleic acid
/ DNA
/ DNA - genetics
/ DNA - metabolism
/ DNA Damage
/ DNA Helicases - genetics
/ DNA Helicases - metabolism
/ DNA Repair
/ DNA Repair Enzymes - genetics
/ DNA Repair Enzymes - metabolism
/ Genomes
/ HEK293 Cells
/ Homologous Recombination
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Localization
/ multidisciplinary
/ Poly-ADP-Ribose Binding Proteins - genetics
/ Poly-ADP-Ribose Binding Proteins - metabolism
/ Protein B
/ Proteins
/ Rad51 Recombinase - genetics
/ Rad51 Recombinase - metabolism
/ Rad52 DNA Repair and Recombination Protein - genetics
/ Rad52 DNA Repair and Recombination Protein - metabolism
/ Rad52 protein
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Ribonucleic acid
/ RNA
/ Science
/ Science (multidisciplinary)
/ Sequence Homology, Amino Acid
/ Transcription
/ Transcription, Genetic
2018
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ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB
Journal Article
ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB
2018
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Overview
Actively transcribed regions of the genome are protected by transcription-coupled DNA repair mechanisms, including transcription-coupled homologous recombination (TC-HR). Here we used reactive oxygen species (ROS) to induce and characterize TC-HR at a transcribed locus in human cells. As canonical HR, TC-HR requires RAD51. However, the localization of RAD51 to damage sites during TC-HR does not require BRCA1 and BRCA2, but relies on RAD52 and Cockayne Syndrome Protein B (CSB). During TC-HR, RAD52 is recruited by CSB through an acidic domain. CSB in turn is recruited by R loops, which are strongly induced by ROS in transcribed regions. Notably, CSB displays a strong affinity for DNA:RNA hybrids in vitro, suggesting that it is a sensor of ROS-induced R loops. Thus, TC-HR is triggered by R loops, initiated by CSB, and carried out by the CSB-RAD52-RAD51 axis, establishing a BRCA1/2-independent alternative HR pathway protecting the transcribed genome.
Transcription-coupled homologous recombination (TC-HR) is activated by reactive oxygen species-induced DNA damage to maintain transcribed genome stability. The authors demonstrate that R loops are induced by ROS at the transcribed genome, triggering a CSB-RAD52- dependent but BRCA1/2-independent RAD51 loading for repair.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13
/ 13/1
/ 13/51
/ 13/89
/ 147/135
/ 38/109
/ 38/15
/ 38/22
/ 38/23
/ 38/77
/ 42/35
/ 82/80
/ 82/83
/ DNA
/ DNA Repair Enzymes - genetics
/ DNA Repair Enzymes - metabolism
/ Genomes
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Poly-ADP-Ribose Binding Proteins - genetics
/ Poly-ADP-Ribose Binding Proteins - metabolism
/ Proteins
/ Rad51 Recombinase - genetics
/ Rad51 Recombinase - metabolism
/ Rad52 DNA Repair and Recombination Protein - genetics
/ Rad52 DNA Repair and Recombination Protein - metabolism
/ Reactive Oxygen Species - metabolism
/ RNA
/ Science
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