Proteomics

Dataset Information

0

DNA replication regulates SPRTN- and Proteasome-dependent DPC proteolysis


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 DPC degradation not only depends on SPRTN but also 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 that together promote replication across immovable protein barriers.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Xenopus Laevis (african Clawed Frog)

TISSUE(S): Egg

SUBMITTER: Mario Oroshi  

LAB HEAD: Matthias Mann

PROVIDER: PXD008831 | Pride | 2019-02-13

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20160223_QEp6_MaRa_SA_mr4p44_01.raw Raw
20160223_QEp6_MaRa_SA_mr4p44_02.raw Raw
20160223_QEp6_MaRa_SA_mr4p44_03.raw Raw
20160223_QEp6_MaRa_SA_mr4p44_04.raw Raw
20160223_QEp6_MaRa_SA_mr4p44_05.raw Raw
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Publications

Replication-Coupled DNA-Protein Crosslink Repair by SPRTN and the Proteasome in Xenopus Egg Extracts.

Larsen Nicolai B NB   Gao Alan O AO   Sparks Justin L JL   Gallina Irene I   Wu R Alex RA   Mann Matthias M   Räschle Markus M   Walter Johannes C JC   Duxin Julien P JP  

Molecular cell 20181227 3


DNA-protein crosslinks (DPCs) are bulky 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 is targeted to DPCs during 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 polyubi  ...[more]

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