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

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

Stable Identifier

R-HSA-5652009

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

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

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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 Povlsen, LK, Beli, P, Wagner, SA, Poulsen, SL, Sylvestersen, KB, Poulsen, JW, Nielsen, ML, Bekker-Jensen, S, Mailand, N, Choudhary, C	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 Hoege, C, Pfander, B, Moldovan, GL, Pyrowolakis, G, Jentsch, S	Nature	2002
24768535	Modification of PCNA by ISG15 plays a crucial role in termination of error-prone translesion DNA synthesis Park, JM, Yang, SW, Yu, KR, Ka, SH, Lee, SW, Seol, JH, Jeon, YJ, Chung, CH	Mol. Cell	2014
20129063	CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis Terai, K, Abbas, T, Jazaeri, AA, Dutta, A	Mol. Cell	2010