Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912153223> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W2912153223 endingPage "645" @default.
- W2912153223 startingPage "645" @default.
- W2912153223 abstract "Abstract Fanconi anemia (FA) is characterized by developmental abnormalities, bone marrow failure, and a strong cancer predisposition. FA cells are hypersensitive to DNA replicative stress, and accumulate co-transcriptional R-loops. Previous work has demonstrated that BRCA2 binds to R loops, and increased R loops are noted in FA-D2 mutant cells. Additionally, it is understood that at least one FA protein, FANCA, binds RNA. The goal of this study was to understand the relationship between FANCD2 and RNA, especially with regard to manifestation of R loops as a part of the pathophysiology of FA. First, we confirmed the increased presence of R loops in FA mutant cells using the S9.6 monoclonal antibody immunofluorescence microscopy. RNAseH overexpression removes R loop signal and increases cell survival upon mitomycin C treatment. We also showed the presence of increased R loops in an actively transcribed region of the actin gene by bisulfite DNA sequencing. We used the Damage At RNA Transcription (DART) assay, which is designed to combine oxidative DNA damage and the genomic insertion of a hyper transcription site (Fig A). Coactivation of transcription and DNA damage results in colocalization of FANCD2 and S9.6/R loop signal at the transcriptional site (Fig B and C). Consistent with the S9.6 IF, wild type RNAseH overexpression resulted in the abrogation of FANCD2 colocalization. We then asked if FANCD2 binds RNA. FANCD2 in cell lysate bound to biotinylated RNA species, preferring GC rich RNAs. Using recombinant FANCI-FANCD2 (ID2) protein (Fig D), we found that ID2 binds preferably to single stranded RNA in a more robust manner than DNA (Fig E and F). Interestingly, an ID2 complex with a known DNA binding mutation in FANCI also was defective for RNA binding. Furthermore, ID2 bound to R loops but was mediated via the single stranded DNA component of the structure. Importantly, an in vitro monoubiquitination reconstitution system using FANCL as the E3 ligase demonstrated that monoubiquitination of ID2 was stimulated to an equal or greater degree by RNA versus DNA, with greater signal in presence of GC-rich, single-stranded RNA as well as R loops (Fig G and H and data not shown). Collectively, our results support a novel mechanism the ID2 complex suppresses the formation of pathogenic R-loops by binding RNA species, thereby activating the FA pathway (Fig I). Figure. Figure. Disclosures No relevant conflicts of interest to declare." @default.
- W2912153223 created "2019-02-21" @default.
- W2912153223 creator A5022759903 @default.
- W2912153223 creator A5044795870 @default.
- W2912153223 creator A5052728382 @default.
- W2912153223 creator A5055861760 @default.
- W2912153223 creator A5059502578 @default.
- W2912153223 creator A5074759619 @default.
- W2912153223 creator A5079834643 @default.
- W2912153223 creator A5084386513 @default.
- W2912153223 creator A5086949270 @default.
- W2912153223 creator A5090899284 @default.
- W2912153223 date "2018-11-29" @default.
- W2912153223 modified "2023-09-30" @default.
- W2912153223 title "FANCI-FANCD2 Binds RNA, Which Stimulates Its Monoubiquitination" @default.
- W2912153223 doi "https://doi.org/10.1182/blood-2018-99-118863" @default.
- W2912153223 hasPublicationYear "2018" @default.
- W2912153223 type Work @default.
- W2912153223 sameAs 2912153223 @default.
- W2912153223 citedByCount "0" @default.
- W2912153223 crossrefType "journal-article" @default.
- W2912153223 hasAuthorship W2912153223A5022759903 @default.
- W2912153223 hasAuthorship W2912153223A5044795870 @default.
- W2912153223 hasAuthorship W2912153223A5052728382 @default.
- W2912153223 hasAuthorship W2912153223A5055861760 @default.
- W2912153223 hasAuthorship W2912153223A5059502578 @default.
- W2912153223 hasAuthorship W2912153223A5074759619 @default.
- W2912153223 hasAuthorship W2912153223A5079834643 @default.
- W2912153223 hasAuthorship W2912153223A5084386513 @default.
- W2912153223 hasAuthorship W2912153223A5086949270 @default.
- W2912153223 hasAuthorship W2912153223A5090899284 @default.
- W2912153223 hasConcept C104317684 @default.
- W2912153223 hasConcept C134935766 @default.
- W2912153223 hasConcept C138885662 @default.
- W2912153223 hasConcept C143425029 @default.
- W2912153223 hasConcept C153911025 @default.
- W2912153223 hasConcept C179926584 @default.
- W2912153223 hasConcept C2776653068 @default.
- W2912153223 hasConcept C2778124228 @default.
- W2912153223 hasConcept C2778993383 @default.
- W2912153223 hasConcept C41895202 @default.
- W2912153223 hasConcept C54355233 @default.
- W2912153223 hasConcept C552990157 @default.
- W2912153223 hasConcept C67705224 @default.
- W2912153223 hasConcept C86803240 @default.
- W2912153223 hasConcept C95444343 @default.
- W2912153223 hasConceptScore W2912153223C104317684 @default.
- W2912153223 hasConceptScore W2912153223C134935766 @default.
- W2912153223 hasConceptScore W2912153223C138885662 @default.
- W2912153223 hasConceptScore W2912153223C143425029 @default.
- W2912153223 hasConceptScore W2912153223C153911025 @default.
- W2912153223 hasConceptScore W2912153223C179926584 @default.
- W2912153223 hasConceptScore W2912153223C2776653068 @default.
- W2912153223 hasConceptScore W2912153223C2778124228 @default.
- W2912153223 hasConceptScore W2912153223C2778993383 @default.
- W2912153223 hasConceptScore W2912153223C41895202 @default.
- W2912153223 hasConceptScore W2912153223C54355233 @default.
- W2912153223 hasConceptScore W2912153223C552990157 @default.
- W2912153223 hasConceptScore W2912153223C67705224 @default.
- W2912153223 hasConceptScore W2912153223C86803240 @default.
- W2912153223 hasConceptScore W2912153223C95444343 @default.
- W2912153223 hasIssue "Supplement 1" @default.
- W2912153223 hasLocation W29121532231 @default.
- W2912153223 hasOpenAccess W2912153223 @default.
- W2912153223 hasPrimaryLocation W29121532231 @default.
- W2912153223 hasRelatedWork W1983750443 @default.
- W2912153223 hasRelatedWork W1997558986 @default.
- W2912153223 hasRelatedWork W2049986951 @default.
- W2912153223 hasRelatedWork W2056946030 @default.
- W2912153223 hasRelatedWork W2121702161 @default.
- W2912153223 hasRelatedWork W2134503721 @default.
- W2912153223 hasRelatedWork W2163773782 @default.
- W2912153223 hasRelatedWork W2593341851 @default.
- W2912153223 hasRelatedWork W2951830765 @default.
- W2912153223 hasRelatedWork W3186377674 @default.
- W2912153223 hasVolume "132" @default.
- W2912153223 isParatext "false" @default.
- W2912153223 isRetracted "false" @default.
- W2912153223 magId "2912153223" @default.
- W2912153223 workType "article" @default.