TY - JOUR
T1 - Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-pkcs
AU - Malu, Shruti
AU - De Ioannes, Pablo
AU - Kozlov, Mikhail
AU - Greene, Marsha
AU - Francis, Dailia
AU - Hanna, Mary
AU - Pena, Jesse
AU - Escalante, Carlos R.
AU - Kurosawa, Aya
AU - Erdjument-Bromage, Hediye
AU - Tempst, Paul
AU - Adachi, Noritaka
AU - Vezzoni, Paolo
AU - Villa, Anna
AU - Aggarwal, Aneel K.
AU - Cortes, Patricia
PY - 2012/5/7
Y1 - 2012/5/7
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20111437
DO - 10.1084/jem.20111437
M3 - Article
C2 - 22529269
AN - SCOPUS:84863798398
SN - 0022-1007
VL - 209
SP - 955
EP - 963
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -