Reactome | KIAA0101 double monoubiquitination

KIAA0101 double monoubiquitination

Stable Identifier

R-HSA-5655193

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

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

KIAA0101 (PAF15) is a PCNA-associated protein expressed during S phase of the cell cycle, under the control of members of the E2F transcription factor family (Chang et al. 2013) and degraded at mitotic exit by the APC:CDH1 complex (Emanuele et al. 2011). KIAA0101 is monoubiquitinated on two lysine residues, K15 and K24, by an unknown ubiquitin ligase. Doubly monoubiquitinated KIAA0101 (PAF15) (MonoUb:K15,K24-KIAA0101) binds PCNA and promotes the switch from translesion DNA synthesis (TLS) polymerase, such as DNA polymerase eta (POLH), to replicative DNA polymerases delta (POLD) or epsilon (POLE). KIAA0101 monoubiquitination thus facilitates termination of TLS and coordinates DNA damage bypass events (Povlsen et al. 2012). UV-induced DNA damage causes removal of MonoUb:K15,K24-KIAA0101 by proteasome-mediated degradation, promoting the switch from replicative DNA polymerase complexes delta (POLD) or epsilon (POLE) to translesion DNA synthesis (TLS) polymerases, such as POLH (DNA polymerase eta) (Povlsen et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
21628590	Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate Elledge, SJ, Elia, AE, Emanuele, MJ, Ciccia, A	Proc. Natl. Acad. Sci. U.S.A.	2011
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
23593430	p15(PAF) is an Rb/E2F-regulated S-phase protein essential for DNA synthesis and cell cycle progression Jeng, YM, Yuan, RH, Chang, CN, Chen, YL, Feng, MJ	PLoS ONE	2013