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Quantitative K-GG site analysis

ABSTRACT: Post-translational modification of proteins by ubiquitin (UQ) and UQ-like modifiers is emerging as a central pathway in DNA replication. We previously showed that chromatin in the vicinity of replisomes is rich in SUMO and depleted in UQ, whereas an opposite pattern is observed in mature chromatin. How this SUMO-rich/UQ-low environment is maintained at replisomes is not known. Here we identify USP7 as a SUMO deubiquitinase that localizes to replication forks and is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 prevents their ubiquitination. Chemical inhibition or genetic deletion of USP7 leads to the accumulation of UQ on SUMOylated proteins, which are displaced from the replisomes. Our findings provide a model to explain the differential accumulation of SUMO and UQ in replication forks versus mature chromatin, and identify an essential role of USP7 that should be taken into account for the use of USP7 inhibitors as anticancer agents.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Colon Cancer

SUBMITTER: Isabel Ruppen

LAB HEAD: Oscar Fernández Capetillo

PROVIDER: PXD002408 | Pride | 2016-01-13

REPOSITORIES: Pride

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			Action	DRS
	20141030_IR_Capetillo_diGly_Control_CID_120m_01.raw	Raw
	20141030_IR_Capetillo_diGly_Control_CID_120m_02.raw	Raw
	20141030_IR_Capetillo_diGly_Control_CID_120m_03.raw	Raw
	20141030_IR_Capetillo_diGly_USP1i_ML_CID_120m_01.raw	Raw
	20141030_IR_Capetillo_diGly_USP1i_ML_CID_120m_02.raw	Raw

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