Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome

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Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome. / Gao, Alan; Larsen, Nicolai; Sparks, Justin; Gallina, Irene; Mann, Matthias; Räschle, Markus; Walter, Johannes; Duxin, Julien.

bioRxiv, 2018.

Research output: Working paper › Preprint › Research

Harvard

Gao, A, Larsen, N, Sparks, J, Gallina, I, Mann, M, Räschle, M, Walter, J & Duxin, J 2018 'Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome' bioRxiv. https://doi.org/10.1101/381889

APA

Gao, A., Larsen, N., Sparks, J., Gallina, I., Mann, M., Räschle, M., Walter, J., & Duxin, J. (2018). Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome. bioRxiv. https://doi.org/10.1101/381889

Vancouver

Gao A, Larsen N, Sparks J, Gallina I, Mann M, Räschle M et al. Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome. bioRxiv. 2018. https://doi.org/10.1101/381889

Author

Gao, Alan ; Larsen, Nicolai ; Sparks, Justin ; Gallina, Irene ; Mann, Matthias ; Räschle, Markus ; Walter, Johannes ; Duxin, Julien. / Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome. bioRxiv, 2018.

Bibtex

@techreport{fbfe68a95a144debaaf7058e5b382ca9,
title = "Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome",
abstract = "DNA-protein crosslinks (DPCs) are bulky DNA lesions that interfere with DNA metabolism and therefore threaten genomic integrity. Recent studies implicate the metalloprotease SPRTN in S-phase removal of DPCs, but how SPRTN activity is coupled to DNA replication is unknown. Using Xenopus egg extracts that recapitulate replication-coupled DPC proteolysis, we show that DPCs can be degraded by SPRTN or the proteasome, which act as independent DPC proteases. Proteasome recruitment requires DPC polyubiquitylation, which is triggered by single-stranded DNA, a byproduct of DNA replication. In contrast, SPRTN-mediated DPC degradation is independent of DPC polyubiquitylation but requires polymerase extension of a nascent strand to the lesion. Thus, SPRTN and proteasome activities are coupled to DNA replication by distinct mechanisms and together promote replication across immovable protein barriers.",
author = "Alan Gao and Nicolai Larsen and Justin Sparks and Irene Gallina and Matthias Mann and Markus R{\"a}schle and Johannes Walter and Julien Duxin",
year = "2018",
doi = "10.1101/381889",
language = "English",
publisher = "bioRxiv",
type = "WorkingPaper",
institution = "bioRxiv",

}

RIS

TY - UNPB

T1 - Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome

AU - Gao, Alan

AU - Larsen, Nicolai

AU - Sparks, Justin

AU - Gallina, Irene

AU - Mann, Matthias

AU - Räschle, Markus

AU - Walter, Johannes

AU - Duxin, Julien

PY - 2018

Y1 - 2018

N2 - DNA-protein crosslinks (DPCs) are bulky DNA lesions that interfere with DNA metabolism and therefore threaten genomic integrity. Recent studies implicate the metalloprotease SPRTN in S-phase removal of DPCs, but how SPRTN activity is coupled to DNA replication is unknown. Using Xenopus egg extracts that recapitulate replication-coupled DPC proteolysis, we show that DPCs can be degraded by SPRTN or the proteasome, which act as independent DPC proteases. Proteasome recruitment requires DPC polyubiquitylation, which is triggered by single-stranded DNA, a byproduct of DNA replication. In contrast, SPRTN-mediated DPC degradation is independent of DPC polyubiquitylation but requires polymerase extension of a nascent strand to the lesion. Thus, SPRTN and proteasome activities are coupled to DNA replication by distinct mechanisms and together promote replication across immovable protein barriers.

AB - DNA-protein crosslinks (DPCs) are bulky DNA lesions that interfere with DNA metabolism and therefore threaten genomic integrity. Recent studies implicate the metalloprotease SPRTN in S-phase removal of DPCs, but how SPRTN activity is coupled to DNA replication is unknown. Using Xenopus egg extracts that recapitulate replication-coupled DPC proteolysis, we show that DPCs can be degraded by SPRTN or the proteasome, which act as independent DPC proteases. Proteasome recruitment requires DPC polyubiquitylation, which is triggered by single-stranded DNA, a byproduct of DNA replication. In contrast, SPRTN-mediated DPC degradation is independent of DPC polyubiquitylation but requires polymerase extension of a nascent strand to the lesion. Thus, SPRTN and proteasome activities are coupled to DNA replication by distinct mechanisms and together promote replication across immovable protein barriers.

U2 - 10.1101/381889

DO - 10.1101/381889

M3 - Preprint

BT - Mechanism of replication-coupled DNA-protein crosslink proteolysis by SPRTN and the proteasome

PB - bioRxiv

ER -

ID: 322792970