SHPRH polyubiquitinates monoubiquitinated PCNA

Stable Identifier
Reaction [omitted]
Homo sapiens
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In response to a stalled replication fork, SHPRH polyubiquitinates lysine-164 of PCNA that has already been monoubiquitinated on lysine-164 by RAD18:UBE2B (RAD18:RAD6) (Unk et al. 2006, Motegi et al. 2006, Motegi et al. 2008). The ubiquitin donor is the E2 complex UBE2N:UBE2V2 (UBC13:MMS2) containing ubiquitin conjugated to UBE2N. The resulting polyubiquitin chain contains lysine-63 (K63) linkages and appears to change the repair process from translesion synthesis (TLS) to template switching (TS). SHPRH interacts directly with PCNA, RAD18:UBE2B, and UBE2N:UBE2V2.
Literature References
PubMed ID Title Journal Year
18719106 Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks

Roest, HP, Ding, H, Motegi, A, Myung, K, Markowitz, SD, Wu, X, Liaw, HJ, Lee, KY, Moinova, H, Hoeijmakers, JH, Maas, A

Proc. Natl. Acad. Sci. U.S.A. 2008
17108083 Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen

Haracska, L, Hurwitz, J, Blastyák, A, Bermudez, V, Prakash, L, Fatyol, K, Hajdu, I, Unk, I, Szakál, B, Prakash, S

Proc. Natl. Acad. Sci. U.S.A. 2006
17130289 Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination

Motegi, A, Myung, K, Markowitz, SD, Sood, R, Liu, PP, Moinova, H

J. Cell Biol. 2006
Catalyst Activity

ubiquitin protein ligase activity of SHPRH:monoUb:K164-PCNA:RAD18:UBE2B:Ub:UBE2N:UBE2V2 [nucleoplasm]

Orthologous Events
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