Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Science
2015 May 01;3486234:1253671. doi: 10.1126/science.1253671.
Show Gene links
Show Anatomy links
DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links.
Räschle M, Smeenk G, Hansen RK, Temu T, Oka Y, Hein MY, Nagaraj N, Long DT, Walter JC, Hofmann K, Storchova Z, Cox J, Bekker-Jensen S, Mailand N, Mann M.
???displayArticle.abstract???
DNA interstrand cross-links (ICLs) block replication fork progression by inhibiting DNA strand separation. Repair of ICLs requires sequential incisions, translesion DNA synthesis, and homologous recombination, but the full set of factors involved in these transactions remains unknown. We devised a technique called chromatin mass spectrometry (CHROMASS) to study protein recruitment dynamics during perturbed DNA replication in Xenopus egg extracts. Using CHROMASS, we systematically monitored protein assembly and disassembly on ICL-containing chromatin. Among numerous prospective DNA repair factors, we identified SLF1 and SLF2, which form a complex with RAD18 and together define a pathway that suppresses genome instability by recruiting the SMC5/6 cohesion complex to DNA lesions. Our study provides a global analysis of an entire DNA repair pathway and reveals the mechanism of SMC5/6 relocalization to damaged DNA in vertebrate cells.
Barlow,
Identification of early replicating fragile sites that contribute to genome instability.
2013, Pubmed
Barlow,
Identification of early replicating fragile sites that contribute to genome instability.
2013,
Pubmed Bekker-Jensen,
Assembly and function of DNA double-strand break repair foci in mammalian cells.
2010,
Pubmed Branzei,
Maintaining genome stability at the replication fork.
2010,
Pubmed Bustard,
During replication stress, non-SMC element 5 (NSE5) is required for Smc5/6 protein complex functionality at stalled forks.
2012,
Pubmed Chan,
Replication stress induces sister-chromatid bridging at fragile site loci in mitosis.
2009,
Pubmed Cox,
Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ.
2014,
Pubmed Dantuma,
A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling.
2006,
Pubmed Deans,
FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia.
2009,
Pubmed Deans,
DNA interstrand crosslink repair and cancer.
2011,
Pubmed De Piccoli,
Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination.
2006,
Pubmed Doil,
RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins.
2009,
Pubmed Helchowski,
A small ubiquitin binding domain inhibits ubiquitin-dependent protein recruitment to DNA repair foci.
2013,
Pubmed Huang,
RAD18 transmits DNA damage signalling to elicit homologous recombination repair.
2009,
Pubmed Hubner,
Quantitative proteomics combined with BAC TransgeneOmics reveals in vivo protein interactions.
2010,
Pubmed Jackson,
The DNA-damage response in human biology and disease.
2009,
Pubmed Jeppsson,
The maintenance of chromosome structure: positioning and functioning of SMC complexes.
2014,
Pubmed Knipscheer,
The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.
2009,
Pubmed
,
Xenbase Kratz,
Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents.
2010,
Pubmed Lee,
Brc1-mediated rescue of Smc5/6 deficiency: requirement for multiple nucleases and a novel Rad18 function.
2007,
Pubmed Leung,
Rtt107 is required for recruitment of the SMC5/6 complex to DNA double strand breaks.
2011,
Pubmed Lin,
SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis.
2011,
Pubmed Liu,
RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA damage.
2012,
Pubmed Long,
BRCA1 promotes unloading of the CMG helicase from a stalled DNA replication fork.
2014,
Pubmed
,
Xenbase Long,
Mechanism of RAD51-dependent DNA interstrand cross-link repair.
2011,
Pubmed
,
Xenbase MacKay,
Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2.
2010,
Pubmed Mailand,
RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins.
2007,
Pubmed Mailand,
Regulation of PCNA-protein interactions for genome stability.
2013,
Pubmed Miyabe,
Rhp51-dependent recombination intermediates that do not generate checkpoint signal are accumulated in Schizosaccharomyces pombe rad60 and smc5/6 mutants after release from replication arrest.
2006,
Pubmed Murray,
Smc5/6: a link between DNA repair and unidirectional replication?
2008,
Pubmed Nagaraj,
System-wide perturbation analysis with nearly complete coverage of the yeast proteome by single-shot ultra HPLC runs on a bench top Orbitrap.
2012,
Pubmed Panier,
Tandem protein interaction modules organize the ubiquitin-dependent response to DNA double-strand breaks.
2012,
Pubmed Pebernard,
The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex.
2006,
Pubmed Räschle,
Mechanism of replication-coupled DNA interstrand crosslink repair.
2008,
Pubmed
,
Xenbase Sale,
Competition, collaboration and coordination--determining how cells bypass DNA damage.
2012,
Pubmed Sheedy,
Brc1-mediated DNA repair and damage tolerance.
2005,
Pubmed Svendsen,
Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair.
2009,
Pubmed Torres-Rosell,
SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions.
2005,
Pubmed Tusher,
Significance analysis of microarrays applied to the ionizing radiation response.
2001,
Pubmed