| http://purl.uniprot.org/citations/21734301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21734301 | http://www.w3.org/2000/01/rdf-schema#comment | "The embryonic ventricular and subventricular zones (VZ/SVZ) contain the neuronal stem and progenitor cells and undergo rapid proliferation. The intermediate zone (IZ) contains nonreplicating, differentiated cells. The VZ/SVZ is hypersensitive to radiation-induced apoptosis. Ablation of DNA non-homologous end-joining (NHEJ) proteins, XRCC4 or DNA ligase IV (LigIV), confers ataxia telangiectasia mutated (ATM)-dependent apoptosis predominantly in the IZ. We examine the mechanistic basis underlying these distinct sensitivities using a viable LigIV (Lig4(Y288C)) mouse, which permits an examination of the DNA damage responses in the embryonic and adult brain. Via combined analysis of DNA breakage, apoptosis, and cell-cycle checkpoint control in tissues, we show that apoptosis in the VZ/SVZ and IZ is activated by low numbers of DNA double-strand breaks (DSBs). Unexpectedly, high sensitivity in the VZ/SVZ arises from sensitive activation of ATM-dependent apoptosis plus an ATM-independent process. In contrast, the IZ appears to be hypersensitive to persistent DSBs. NHEJ functions efficiently in both compartments. The VZ/SVZ and IZ regions incur high endogenous DNA breakage, which correlates with VZ proliferation. We demonstrate a functional G(2)/M checkpoint in VZ/SVZ cells and show that it is not activated by low numbers of DSBs, allowing damaged VZ/SVZ cells to transit into the IZ. We propose a novel model in which microcephaly in LIG4 syndrome arises from sensitive apoptotic induction from persisting DSBs in the IZ, which arise from high endogenous breakage in the VZ/SVZ and transit of damaged cells to the IZ. The VZ/SVZ, in contrast, is highly sensitive to acute radiation-induced DSB formation."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.1324-11.2011"xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Liu C."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Hoffmann E."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Carr A.M."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Ju L."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Jeggo P.A."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Gruber R."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Wang Z.Q."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/author | "Gatz S.A."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/name | "J Neurosci"xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/pages | "10088-10100"xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/title | "Requirement for DNA ligase IV during embryonic neuronal development."xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://purl.uniprot.org/core/volume | "31"xsd:string |
| http://purl.uniprot.org/citations/21734301 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21734301 |
| http://purl.uniprot.org/citations/21734301 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21734301 |
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| http://purl.uniprot.org/uniprot/#_D3Z0Q2-mappedCitation-21734301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21734301 |
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| http://purl.uniprot.org/uniprot/#_F7CE65-mappedCitation-21734301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21734301 |
| http://purl.uniprot.org/uniprot/#_A2AU90-mappedCitation-21734301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21734301 |
| http://purl.uniprot.org/uniprot/#_P70399-mappedCitation-21734301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21734301 |
| http://purl.uniprot.org/uniprot/#_B9EHX4-mappedCitation-21734301 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21734301 |