TY - JOUR
T1 - RNF8 and RNF168 but not HERC2 are required for DNA damage-induced ubiquitylation in chicken DT40 cells
AU - Oestergaard, Vibe H.
AU - Pentzold, Constanze
AU - Pedersen, Rune Troelsgaard
AU - Iosif, Silviu
AU - Alpi, Arno
AU - Bekker-Jensen, Simon
AU - Mailand, Niels
AU - Lisby, Michael
PY - 2012
Y1 - 2012
N2 - The ubiquitylation cascade plays an important role in the recruitment of repair factors at DNA double-strand breaks. The involvement of a growing number of ubiquitin E3 ligases adds to the complexity of the DNA damage-induced ubiquitin signaling. Here we use the genetically tractable avian cell line DT40 to investigate the role of HERC2, RNF8 and RNF168 in the DNA damage-induced ubiquitylation pathway. We show that formation of ubiquitin foci as well as cell survival after DNA damage depends on both RNF8 and RNF168. However, we find that RNF8 and RNF168 knockout cell lines respond differently to treatment with camptothecin indicating that they do not function in a strictly linear manner. Surprisingly, we show that HERC2 is required neither for survival nor for ubiquitin foci formation after DNA damage in DT40. Moreover, the E3 ubiquitin ligase activity of HERC2 is not redundant to that of RNF8 or RNF168. (C) 2012 Elsevier B.V. All rights reserved.
AB - The ubiquitylation cascade plays an important role in the recruitment of repair factors at DNA double-strand breaks. The involvement of a growing number of ubiquitin E3 ligases adds to the complexity of the DNA damage-induced ubiquitin signaling. Here we use the genetically tractable avian cell line DT40 to investigate the role of HERC2, RNF8 and RNF168 in the DNA damage-induced ubiquitylation pathway. We show that formation of ubiquitin foci as well as cell survival after DNA damage depends on both RNF8 and RNF168. However, we find that RNF8 and RNF168 knockout cell lines respond differently to treatment with camptothecin indicating that they do not function in a strictly linear manner. Surprisingly, we show that HERC2 is required neither for survival nor for ubiquitin foci formation after DNA damage in DT40. Moreover, the E3 ubiquitin ligase activity of HERC2 is not redundant to that of RNF8 or RNF168. (C) 2012 Elsevier B.V. All rights reserved.
U2 - 10.1016/j.dnarep.2012.08.005
DO - 10.1016/j.dnarep.2012.08.005
M3 - Article
C2 - 23010445
SN - 1568-7864
VL - 11
SP - 892
EP - 905
JO - DNA Repair
JF - DNA Repair
IS - 11
ER -