http://purl.uniprot.org/citations/34006647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/34006647 | http://www.w3.org/2000/01/rdf-schema#comment | "Classical nonhomologous end joining (C-NHEJ) repairs DNA double-strand breaks (DSBs) throughout interphase but predominates in G1 phase when homologous recombination is unavailable. Complexes containing the Ku70/80 ("Ku") and XRCC4/ligase IV (Lig4) core C-NHEJ factors are required, respectively, for sensing and joining DSBs. While XRCC4/Lig4 are absolutely required for joining RAG1/2 endonuclease ("RAG")-initiated DSBs during V(D)J recombination in G1-phase progenitor lymphocytes, cycling cells deficient for XRCC4/Lig4 also can join chromosomal DSBs by alternative end-joining (A-EJ) pathways. Restriction of V(D)J recombination by XRCC4/Lig4-mediated joining has been attributed to RAG shepherding V(D)J DSBs exclusively into the C-NHEJ pathway. Here, we report that A-EJ of DSB ends generated by RAG1/2, Cas9:gRNA, and Zinc finger endonucleases in Lig4-deficient G1-arrested progenitor B cell lines is suppressed by Ku. Thus, while diverse DSBs remain largely as free broken ends in Lig4-deficient G1-arrested progenitor B cells, deletion of Ku70 increases DSB rejoining and translocation levels to those observed in Ku70-deficient counterparts. Correspondingly, while RAG-initiated V(D)J DSB joining is abrogated in Lig4-deficient G1-arrested progenitor B cell lines, joining of RAG-generated DSBs in Ku70-deficient and Ku70/Lig4 double-deficient lines occurs through a translocation-like A-EJ mechanism. Thus, in G1-arrested, Lig4-deficient progenitor B cells are functionally end-joining suppressed due to Ku-dependent blockage of A-EJ, potentially in association with G1-phase down-regulation of Lig1. Finally, we suggest that differential impacts of Ku deficiency versus Lig4 deficiency on V(D)J recombination, neuronal apoptosis, and embryonic development results from Ku-mediated inhibition of A-EJ in the G1 cell cycle phase in Lig4-deficient developing lymphocyte and neuronal cells."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2103630118"xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Hu J."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Kumar V."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Lou J."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Liang Z."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Ye A.Y."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Alt F.W."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Lin S.G."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Zurita J."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Frock R.L."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Boboila C."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Le Bouteiller M."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/author | "Kenrick J."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/pages | "e2103630118"xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/title | "Ku70 suppresses alternative end joining in G1-arrested progenitor B cells."xsd:string |
http://purl.uniprot.org/citations/34006647 | http://purl.uniprot.org/core/volume | "118"xsd:string |
http://purl.uniprot.org/citations/34006647 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34006647 |
http://purl.uniprot.org/citations/34006647 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34006647 |
http://purl.uniprot.org/uniprot/#_B2RDN9-mappedCitation-34006647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34006647 |
http://purl.uniprot.org/uniprot/#_B4DE32-mappedCitation-34006647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34006647 |
http://purl.uniprot.org/uniprot/#_B1AHC9-mappedCitation-34006647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34006647 |