DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage

E.J. Davis, C. Lachaud, P. Appleton, T.J. MacArtney, Inke Nathke, J. Rouse

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Ubiquitin-binding domains (UBDs) are crucial for recruiting many proteins to sites of DNA damage. Here we characterize C1orf124 (Spartan; referred to as DVC1), which has an UBZ4-type UBD found predominantly in DNA repair proteins. DVC1 associates with DNA replication factories and localizes to sites of DNA damage in human cells, in a manner that requires the ability of the DVC1 UBZ domain to bind to ubiquitin polymers in vitro and a conserved PCNA-interacting motif. DVC1 interacts with the p97 protein 'segregase'. We show that DVC1 recruits p97 to sites of DNA damage, where we propose that p97 facilitates the extraction of the translesion synthesis (TLS) polymerase (Pol) ? during DNA repair to prevent excessive TLS and limit the incidence of mutations induced by DNA damage. We introduce DVC1 as a regulator of cellular responses to DNA damage that prevents mutations when DNA damage occurs.
Original languageEnglish
Pages (from-to)1093-1100
Number of pages8
JournalNature Structural & Molecular Biology
Volume19
Issue number11
DOIs
Publication statusPublished - 2012

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DNA Damage
Ubiquitin
Proteins
DNA Repair
Mutation
Proliferating Cell Nuclear Antigen
DNA Replication
Polymers
Incidence

Cite this

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abstract = "Ubiquitin-binding domains (UBDs) are crucial for recruiting many proteins to sites of DNA damage. Here we characterize C1orf124 (Spartan; referred to as DVC1), which has an UBZ4-type UBD found predominantly in DNA repair proteins. DVC1 associates with DNA replication factories and localizes to sites of DNA damage in human cells, in a manner that requires the ability of the DVC1 UBZ domain to bind to ubiquitin polymers in vitro and a conserved PCNA-interacting motif. DVC1 interacts with the p97 protein 'segregase'. We show that DVC1 recruits p97 to sites of DNA damage, where we propose that p97 facilitates the extraction of the translesion synthesis (TLS) polymerase (Pol) ? during DNA repair to prevent excessive TLS and limit the incidence of mutations induced by DNA damage. We introduce DVC1 as a regulator of cellular responses to DNA damage that prevents mutations when DNA damage occurs.",
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DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage. / Davis, E.J.; Lachaud, C.; Appleton, P.; MacArtney, T.J.; Nathke, Inke; Rouse, J.

In: Nature Structural & Molecular Biology, Vol. 19, No. 11, 2012, p. 1093-1100.

Research output: Contribution to journalArticle

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AU - Lachaud, C.

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