RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA

Stable Identifier
Reaction [transition]
Homo sapiens
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The complex of RAD18, an E3 ubiquitin ligase, and UBE2B (RAD6), an E2 ubiquitin conjugating enzyme, monoubiquitinates PCNA associated with damaged DNA on lysine residue K164, using the ubiquitin residue K63 to create the covalent bond (Hoege et al. 2002). The catalytic subunit of DNA polymerase delta (POLD), POLD1, does not bind monoubiquitinated PCNA (Park et al. 2014), implying that replicative polymerases POLD and POLE (DNA polymerase epsilon complex) dissociate from PCNA monubiquitinated at K164. This is in accordance with the proposed DNA polymerase switch during translesion DNA synthesis (TLS) (Friedberg et al. 2005). DNA damage induced removal of PCNA-associated protein KIAA0101 (PAF15) through proteasome-mediated degradation facilitates switching from replicative DNA polymerases POLD and POLE to TLS polymerases (Povlsen et al. 2012).

The ubiquitin ligase complex RBX1:CUL4:DDB1:DTL can also monoubiquitinate PCNA. RBX1:CUL4:DDB1:DTL is probably responsible for the basal monoubiquitination of PCNA and may contribute to the kinetics of DNA-damage induced PCNA monoubiquitination (Terai et al. 2010).

Literature References
PubMed ID Title Journal Year
23000965 Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass

Nielsen, ML, Poulsen, SL, Sylvestersen, KB, Beli, P, Choudhary, C, Povlsen, LK, Bekker-Jensen, S, Mailand, N, Poulsen, JW, Wagner, SA

Nat. Cell Biol. 2012
15916957 Trading places: how do DNA polymerases switch during translesion DNA synthesis?

Friedberg, EC, Lehmann, AR, Fuchs, RP

Mol. Cell 2005
12226657 RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO

Moldovan, GL, Hoege, C, Pfander, B, Pyrowolakis, G, Jentsch, S

Nature 2002
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
20129063 CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis

Abbas, T, Dutta, A, Terai, K, Jazaeri, AA

Mol. Cell 2010
Catalyst Activity

ubiquitin-protein transferase activity of RAD18:UBE2B,RBX1:CUL4:DDB1:DTL:PCNA:POLD,POLE:RPA:RFC:Damaged DNA Template [nucleoplasm]

Orthologous Events
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