RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks
Andrew E. H. Elia,David C. Wang,David C. Wang,Nicholas A. Willis,Alexander P. Boardman,Alexander P. Boardman,Ildiko Hajdu,Richard O. Adeyemi,Elizabeth Lowry,Elizabeth Lowry,Steven P. Gygi,Ralph Scully,Stephen J. Elledge +12 more
TLDR
It is demonstrated that RPA, which functions as a protein scaffold in the replication stress response, is multiply ubiquitinated upon replication fork stalling, and mutations suggest that multisite ubiquitination of the entire RPA complex is responsible for repair at stalled forks.About:
This article is published in Molecular Cell.The article was published on 2015-10-15 and is currently open access. It has received 95 citations till now. The article focuses on the topics: Replication protein A & Minichromosome maintenance.read more
Citations
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Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers
TL;DR: Findings have revealed compelling insights into the complex mechanisms by which ubiquitin and UBLs regulate protein interactions with DSB sites to promote accurate lesion repair and protection of genome integrity in mammalian cells, and offer new therapeutic opportunities for diseases linked to genetic instability.
Journal ArticleDOI
The Fanconi Anemia Pathway in Cancer.
TL;DR: The current understanding of the functions of the FA pathway in the maintenance of genomic stability is discussed, and an overview of the prevalence and clinical relevance of somatic mutations in FA genes is presented.
Journal ArticleDOI
Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia
Kerstin Knies,Shojiro Inano,María José Ramírez,Masamichi Ishiai,Jordi Surrallés,Jordi Surrallés,Minoru Takata,Detlev Schindler +7 more
TL;DR: RFWD3 is proposed as an FA gene, FANCW, supported by cellular paradigm systems and an animal model and the cellular phenotype was mirrored in genetically engineered human and avian cells by inactivation of RFWD3 or introduction of the patient-derived missense mutation.
Journal ArticleDOI
Multiomic Analysis of the UV-Induced DNA Damage Response.
Stefan Boeing,Laura Williamson,Vesela Encheva,Ilaria Gori,Rebecca E. Saunders,Rachael Instrell,Ozan Aygün,Marta Rodríguez-Martínez,Juston C. Weems,Gavin Kelly,Joan W. Conaway,Joan W. Conaway,Ronald C. Conaway,Ronald C. Conaway,Aengus Stewart,Michael Howell,Ambrosius P. Snijders,Jesper Q. Svejstrup +17 more
TL;DR: A role for the poorly studied, melanoma-associated serine/threonine kinase 19 (STK19) is uncovered, which provides a systems-wide overview of the diverse cellular processes connected to the transcription-related DNA damage response.
Journal ArticleDOI
Functions, Regulation, and Therapeutic Implications of the ATR Checkpoint Pathway
Stephanie A. Yazinski,Lee Zou +1 more
TL;DR: Understanding ATR signaling and modulation is essential to unraveling which tumors have increased dependence on AtR signaling as well as how the ATR pathway can best be exploited for targeted cancer therapy.
References
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Journal ArticleDOI
The DNA Damage Response: Making It Safe to Play with Knives
TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
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Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Lee Zou,Stephen J. Elledge +1 more
TL;DR: The data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling.
Journal ArticleDOI
Causes and consequences of replication stress.
TL;DR: In this paper, the kinase ATR (ATM- and Rad3-related) stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability.
Journal ArticleDOI
RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair Proteins
Niels Mailand,Simon Bekker-Jensen,Helene Faustrup,Fredrik Melander,Jiri Bartek,Claudia Lukas,Jiri Lukas +6 more
TL;DR: It is suggested that MDC1-mediated and RNF8-executed histone ubiquitylation protects genome integrity by licensing the DSB-flanking chromatin to concentrate repair factors near the DNA lesions.
Journal ArticleDOI
RNF8 Transduces the DNA-Damage Signal via Histone Ubiquitylation and Checkpoint Protein Assembly.
Michael S.Y. Huen,Robert A. Grant,Isaac A. Manke,Kay Minn,Xiaochun Yu,Michael B. Yaffe,Junjie Chen +6 more
TL;DR: This study implicates RNF8 as a novel DNA-damage-responsive protein that integrates protein phosphorylation and ubiquitylation signaling and plays a critical role in the cellular response to genotoxic stress.
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