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Distinct effects of DNA-PKcs and Artemis inactivation on signal joint formation in vivo
- Source :
- Molecular Immunology, Molecular Immunology, 2008, 45 (12), pp.3383-3391, Molecular Immunology, Elsevier, 2008, 45 (12), pp.3383-91. 〈10.1016/j.molimm.2008.04.004〉, Molecular Immunology, Elsevier, 2008, 45 (12), pp.3383-91. ⟨10.1016/j.molimm.2008.04.004⟩, Molecular Immunology, 2008, 45 (12), pp.3383-91. ⟨10.1016/j.molimm.2008.04.004⟩, Molecular Immunology, Elsevier, 2008, 45 (12), pp.3383-3391
- Publication Year :
- 2008
- Publisher :
- HAL CCSD, 2008.
-
Abstract
- International audience; The assembly of functional immune receptor genes via V(D)J recombination in developing lymphocytes generates DNA double-stranded breaks intermediates that are repaired by non-homologous end joining (NHEJ). This repair pathway requires the sequential recruitment and activation onto coding and signal DNA ends of several proteins, including the DNA-dependent protein kinase and the nuclease Artemis. Artemis activity, triggered by the DNA-dependent protein kinase, is necessary to process the genes hairpin-sealed coding ends but appears dispensable for the ligation of the reciprocal phosphorylated, blunt-ended signal ends into a signal joint. The DNA-dependent protein kinase is however present on signal ends and could potentially recruit and activate Artemis during signal joint formation. To determine whether Artemis plays a role during the resolution of signal ends during V(D)J recombination, we analyzed the structure of signal joints generated in developing thymocytes during the rearrangement of T cell receptor genes in wild type mice and mice mutated for NHEJ factors. These joints exhibit junctional diversity resulting from N nucleotide polymerization by the terminal nucleotidyl transferase and nucleotide loss from one or both of the signal ends before they are ligated. Our results show that Artemis participates in the repair of signal ends in vivo. Furthermore, our results also show that while the DNA-dependent protein kinase complex protects signal ends from processing, including deletions, Artemis seems on the opposite to promote their accessibility to modifying enzymes. In addition, these data suggest that Artemis might be the nuclease responsible for nucleotide loss from signal ends during the repair process.
- Subjects :
- Protein kinase complex
MESH : Molecular Sequence Data
MESH : DNA
MESH : Lymphocytes
DNA-Activated Protein Kinase
Mice, SCID
MESH: Base Sequence
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Artemis
Mice
0302 clinical medicine
MESH: Endonucleases
MESH : Antigens, Nuclear
MESH : Endonucleases
[ SDV.IMM ] Life Sciences [q-bio]/Immunology
MESH: Animals
Lymphocytes
MESH: Mice, SCID
MESH : DNA-Activated Protein Kinase
DNA-PKcs
ComputingMilieux_MISCELLANEOUS
0303 health sciences
biology
V(D)J recombination
MESH: DNA
Nuclear Proteins
Antigens, Nuclear
T cell receptor genes
Junctional diversity
DNA-Binding Proteins
Non-homologous end joining
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology
[SDV.IMM]Life Sciences [q-bio]/Immunology
MESH : DNA-Binding Proteins
MESH: Enzyme Activation
[SDV.IMM] Life Sciences [q-bio]/Immunology
Molecular Sequence Data
Immunology
MESH : Mice, Inbred C57BL
03 medical and health sciences
MESH: Mice, Inbred C57BL
signal joints
MESH : Mice
Animals
Protein kinase A
MESH: Antigens, Nuclear
MESH: Mice
Ku Autoantigen
Molecular Biology
030304 developmental biology
Nuclease
MESH: Molecular Sequence Data
Base Sequence
MESH : Nuclear Proteins
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
DNA
Endonucleases
Molecular biology
MESH : Mice, SCID
Enzyme Activation
Mice, Inbred C57BL
MESH: DNA-Activated Protein Kinase
biology.protein
MESH: Lymphocytes
MESH : Base Sequence
MESH : Animals
Homologous recombination
MESH : Enzyme Activation
MESH: Nuclear Proteins
MESH: DNA-Binding Proteins
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 01615890
- Database :
- OpenAIRE
- Journal :
- Molecular Immunology, Molecular Immunology, 2008, 45 (12), pp.3383-3391, Molecular Immunology, Elsevier, 2008, 45 (12), pp.3383-91. 〈10.1016/j.molimm.2008.04.004〉, Molecular Immunology, Elsevier, 2008, 45 (12), pp.3383-91. ⟨10.1016/j.molimm.2008.04.004⟩, Molecular Immunology, 2008, 45 (12), pp.3383-91. ⟨10.1016/j.molimm.2008.04.004⟩, Molecular Immunology, Elsevier, 2008, 45 (12), pp.3383-3391
- Accession number :
- edsair.doi.dedup.....cf2d5484d5904194fcef3fc03897ada8