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

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

Stable Identifier

R-HSA-5654989

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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

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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