SPRTN:VCP-mediated release of POLH from monoUb:K164-PCNA

Stable Identifier
Reaction [transition]
Homo sapiens
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The ATP-ase activity of VCP facilitates release of POLH (DNA polymerase eta) from monoubiquitinated PCNA (MonoUb:K164-PCNA) at DNA damage sites, thus ending POLH-mediated translesion DNA synthesis (TLS) (Davis et al. 2012, Mosbech et al. 2012). Although conjugation of the ubiquitin-like protein ISG15 to PCNA has been found to terminate POLH-dependent TLS, the SPRTN:VCP complex has been implicated in serving as an alternative termination pathway (Park et al. 2014). Since VCP has been found to undergo ISGylation (Giannakopoulos et al. 2005), it remains to be determined whether SPRTN, VCP and the ISG15-conjugating system function in the same TLS-regulatory pathway or two separate pathways.

Literature References
PubMed ID Title Journal Year
16139798 Proteomic identification of proteins conjugated to ISG15 in mouse and human cells

Virgin, HW, Zhang, DE, Jacobs, BS, Luo, JK, Borden, EC, Papov, V, Li, J, Zou, W, Lenschow, DJ, Giannakopoulos, NV

Biochem Biophys Res Commun 2005
23042607 DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage

Davis, EJ, Lachaud, C, Näthke, I, Appleton, P, Rouse, J, Macartney, TJ

Nat. Struct. Mol. Biol. 2012
24768535 Modification of PCNA by ISG15 plays a crucial role in termination of error-prone translesion DNA synthesis

Lee, SW, Seol, JH, Yang, SW, Yu, KR, Park, JM, Ka, SH, Jeon, YJ, Chung, CH

Mol. Cell 2014
23042605 DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks

Hartmann-Petersen, R, Lukas, J, Beli, P, Lukas, C, Choudhary, C, Gibbs-Seymour, I, Bekker-Jensen, S, Mailand, N, Pocock, R, Mosbech, A, Povlsen, L, Smedegaard, S, Nielsen, SV, Kagias, K, Sedgwick, G, Thorslund, T

Nat. Struct. Mol. Biol. 2012
Catalyst Activity

ATP hydrolysis activity of NPLOC4:UFD1L:VCP:SPRTN:POLH:MonoUb:K164-PCNA:RPA:RFC:(TT-CPD:AA-polydNMP)-DNA Template [nucleoplasm]

Orthologous Events
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