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J Biol Chem 2022 Aug 01;2988:102234. doi: 10.1016/j.jbc.2022.102234.
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The p97 segregase cofactor Ubxn7 facilitates replisome disassembly during S-phase.

Tarcan Z , Poovathumkadavil D , Skagia A , Gambus A .

Complex cellular processes are driven by the regulated assembly and disassembly of large multiprotein complexes. While we are beginning to understand the molecular mechanism for assembly of the eukaryotic DNA replication machinery (replisome), we still know relatively little about the regulation of its disassembly at replication termination. Recently, the first elements of this process have emerged, revealing that the replicative helicase, at the heart of the replisome, is polyubiquitylated prior to unloading and that this unloading requires p97 segregase activity. Two different E3 ubiquitin ligases have now been shown to ubiquitylate the helicase under different conditions: Cul2Lrr1 and TRAIP. Here, using Xenopus laevis egg extract cell-free system and biochemical approaches, we have found two p97 cofactors, Ubxn7 and Faf1, which can interact with p97 during replisome disassembly during S-phase. We show only Ubxn7, however, facilitates efficient replisome disassembly. Ubxn7 delivers this role through its interaction via independent domains with both Cul2Lrr1 and p97 to allow coupling between Mcm7 ubiquitylation and its removal from chromatin. Our data therefore characterize Ubxn7 as the first substrate-specific p97 cofactor regulating replisome disassembly in vertebrates and a rationale for the efficacy of the Cul2Lrr1 replisome unloading pathway in unperturbed S-phase.

PubMed ID: 35798141
Article link: J Biol Chem
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: atm atr cdc45 chek1 cpsf2 cul2 eif4g2 faf1 gins2 mcm7 pcna ubxn7
GO keywords: DNA replication [+]
Antibodies: Cul2 Ab1 GINS Ab1 Pcna Ab5

Article Images: [+] show captions
References [+] :
Alexandru, UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover. 2008, Pubmed