Reactome | HLTF polyubiquitinates monoubiquitinated PCNA

HLTF polyubiquitinates monoubiquitinated PCNA

Stable Identifier

R-HSA-8943040

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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HLTF polyubiquitinates monoubiquitinated PCNA

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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
21396873	SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis Chen, JY, Zeman, MK, Yee, MC, Cimprich, KA, Lin, JR	Mol. Cell	2011
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
19723507	Biochemical characterisation of the SWI/SNF family member HLTF Toth, R, Rouse, J, MacKay, C	Biochem. Biophys. Res. Commun.	2009
26350214	Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling Haracska, L, Venclovas, Č, Gali, H, Balogh, D, Neculai, D, Dhe-Paganon, S, Achar, YJ, Juhasz, S, Morocz, M	Nucleic Acids Res.	2015
18316726	Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination Haracska, L, Hurwitz, J, Prakash, L, Fatyol, K, Yoon, JH, Hajdu, I, Unk, I, Prakash, S	Proc. Natl. Acad. Sci. U.S.A.	2008