DCLRE1C (ARTEMIS) processes DNA DSB ends

Stable Identifier
Reaction [transition]
Homo sapiens
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DCLRE1C (ARTEMIS) possesses an intrinsic 5' to 3' exonuclease activity. Upon binding to PRKDC (DNA-PKcs) at DNA double strand breaks (DSBs) and undergoing PRKDC-mediated phosphorylation, DCLRE1C acquires endonucleolytic activity towards 5' and 3' overhangs at DNA double strand breaks, and it also acquires a hairpin opening activity (Ma et al. 2002, Ma et al. 2005). Autophosphorylation of PRKDC, although not required for the kinase activity of PRKDC, is needed for the activation of the endonucleolytic activity of DCLRE1C, probably by inducing a conformational change in PRKDC that provides DCLRE1C with access to DNA ends (Goodarzi et al. 2006, Niewolik et al. 2006, Jiang et al. 2015).
Literature References
PubMed ID Title Journal Year
25818648 Differential Phosphorylation of DNA-PKcs Regulates the Interplay between End-Processing and End-Ligation during Nonhomologous End-Joining

Zha, S, Crowe, JL, Dubois, RL, Nakajima, S, Lan, L, Liu, C, Yu, X, Liu, X, Li, C, Wang, Y, Lee, BJ, Jiang, W

Mol. Cell 2015
16874298 DNA-PK autophosphorylation facilitates Artemis endonuclease activity

Ye, R, Härer, C, Walker, SA, Douglas, P, Marchetti, C, Lees-Miller, SP, Jeggo, PA, Goodarzi, AA, Morrice, N, Riballo, E, Yu, Y

EMBO J. 2006
16093244 The DNA-dependent protein kinase catalytic subunit phosphorylation sites in human Artemis

Lieber, MR, Schwarz, K, Lu, H, Pannicke, U, Niewolik, D, Ma, Y

J. Biol. Chem. 2005
16914548 DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5' or 3' overhangs

Kulesza, P, Schwarz, K, Lieber, MR, Lu, H, Wang, LC, Pannicke, U, Zandi, E, Niewolik, D, Ma, Y

J. Biol. Chem. 2006
11955432 Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination.

Schwarz, K, Pannicke, U, Lieber, MR, Ma, Y

Cell 2002
Catalyst Activity

endonuclease activity of p-T2609,S2612,T2638,T2647-PRKDC:XRCC5:XRCC6:p-S516,S645-DCLRE1C:DNA DSB ends [nucleoplasm]

Orthologous Events
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