HLTF polyubiquitinates monoubiquitinated PCNA

Stable Identifier
Reaction [omitted]
Homo sapiens
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In response to a stalled replication fork, HLTF polyubiquitinates lysine-164 of PCNA that has already been monoubiquitinated on lysine-164 by RAD18:UBE2B (RAD18:RAD6) (Unk et al. 2008, Motegi et al. 2008, MacKay et al. 2009, Achar et al. 2015). 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). HLTF interacts directly with PCNA, RAD18:UBE2B, and UBE2N:UBE2V2. HLTF and SHPRH are not completely redundant: HLTF is involved in repair of DNA lesions created by ultraviolet light while SHPRH is involved in repair of lesions created by methylmethane sulfonate (Lin et al. 2011). Despite the polyubiquitination activity of HLTF, in vivo HLTF appears to increase monoubiquitination of PCNA (Lin et al. 2011).

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

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

Proc. Natl. Acad. Sci. U.S.A. 2008
21396873 SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis

Lin, JR, Zeman, MK, Chen, JY, Yee, MC, Cimprich, KA

Mol. Cell 2011
19723507 Biochemical characterisation of the SWI/SNF family member HLTF

MacKay, C, Toth, R, Rouse, J

Biochem. Biophys. Res. Commun. 2009
26350214 Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

Achar, YJ, Balogh, D, Neculai, D, Juhasz, S, Morocz, M, Gali, H, Dhe-Paganon, S, Venclovas, Č, Haracska, L

Nucleic Acids Res. 2015
18316726 Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination

Unk, I, Hajdu, I, Fatyol, K, Hurwitz, J, Yoon, JH, Prakash, L, Prakash, S, Haracska, L

Proc. Natl. Acad. Sci. U.S.A. 2008
Catalyst Activity

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

Orthologous Events
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