Proteomics

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SPOP promotes transcriptional expression of DNA repair and replication factors to prevent replication stress and genomic instability.


ABSTRACT: Mutations in SPOP, the gene most frequently point-mutated in primary prostate cancer, are associated with a high degree of genomic instability and deficiency in homologous recombination repair of DNA but the underlying mechanisms. SPOP knockdown leads to spontaneous replication stress and impaired recovery from replication fork stalling. An SPOP interactome analysis shows that wild type (WT) SPOP but not mutant SPOP associates with multiple proteins involved in transcription, mRNA splicing and export. Consistent with the association of SPOP with transcription, splicing and RNA export complexes, the decreased expression of several components of the DNA damage response pathway occurs at the level of transcription.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell Of Prostate, Epithelial Cell, Prostate Cancer Cell

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Diego Iglesias-Gato  

LAB HEAD: Diego Iglesias-Gato

PROVIDER: PXD010527 | Pride | 2018-08-21

REPOSITORIES: Pride

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Publications

SPOP promotes transcriptional expression of DNA repair and replication factors to prevent replication stress and genomic instability.

Hjorth-Jensen Kim K   Maya-Mendoza Apolinar A   Dalgaard Nanna N   Sigurðsson Jón O JO   Bartek Jiri J   Iglesias-Gato Diego D   Olsen Jesper V JV   Flores-Morales Amilcar A  

Nucleic acids research 20181001 18


Mutations in SPOP, the gene most frequently point-mutated in primary prostate cancer, are associated with a high degree of genomic instability and deficiency in homologous recombination repair of DNA but the underlying mechanisms behind this defect are currently unknown. Here we demonstrate that SPOP knockdown leads to spontaneous replication stress and impaired recovery from replication fork stalling. We show that this is associated with reduced expression of several key DNA repair and replicat  ...[more]

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