Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-pkcs Journal Article
| Authors: | Malu, S.; De Ioannes, P.; Kozlov, M.; Greene, M.; Francis, D.; Hanna, M.; Pena, J.; Escalante, C. R.; Kurosawa, A.; Erdjument-Bromage, H.; Tempst, P.; Adachi, N.; Vezzoni, P.; Villa, A.; Aggarwal, A. K.; Cortes, P. |
| Article Title: | Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-pkcs |
| Abstract: | Artemis is an endonuclease that opens coding hairpin ends during V(D)J recombination and has critical roles in postirradiation cell survival. A direct role for the C-terminal region of Artemis in V(D)J recombination has not been defined, despite the presence of immunodeficiency and lymphoma development in patients with deletions in this region. Here, we report that the Artemis C-terminal region directly interacts with the DNA-binding domain of Ligase IV, a DNA Ligase which plays essential roles in DNA repair and V(D)J recombination. The Artemis-Ligase IV interaction is specific and occurs independently of the presence of DNA and DNA-protein kinase catalytic subunit (DNA-PKcs), another protein known to interact with the Artemis C-terminal region. Point mutations in Artemis that disrupt its interaction with Ligase IV or DNA-PKcs reduce V(D)J recombination, and Artemis mutations that affect interactions with Ligase IV and DNA-PKcs show additive detrimental effects on coding joint formation. Signal joint formation remains unaffected. Our data reveal that the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Ligase IV and DNA-PKcs. © 2012 Malu et al. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; unclassified drug; dna binding protein; human cell; promoter region; sequence analysis; genetics; dna-binding proteins; nonhuman; molecular genetics; protein domain; protein function; mass spectrometry; metabolism; dna repair; nuclear protein; carboxy terminal sequence; protein protein interaction; in vitro study; fluorescence polarization; hela cell; hela cells; transfection; mutational analysis; phosphorylation; physiology; gene vector; genetic vectors; nuclear proteins; amino acid sequence; molecular sequence data; genetic transfection; glioblastoma; nucleotide sequence; glutathione transferase; immunoprecipitation; base sequence; dna sequence; catalysis; dna primers; primer dna; endonuclease; xrcc4 protein; point mutation; structure analysis; polydeoxyribonucleotide synthase; protein kinase; dna ligases; sequence analysis, dna; v(d)j recombination; dna dependent protein kinase; dna-activated protein kinase; polydeoxyribonucleotide synthase (atp); dclre1c protein, human; prkdc protein, human; xrcc4 protein, human; vdj recombination; protein artemis |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 209 |
| Issue: | 5 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2012-05-07 |
| Start Page: | 955 |
| End Page: | 963 |
| Language: | English |
| DOI: | 10.1084/jem.20111437 |
| PROVIDER: | scopus |
| PMCID: | PMC3348108 |
| PUBMED: | 22529269 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 24 August 2012" - "CODEN: JEMEA" - "Source: Scopus" |
