PXD001736

PXD001736 is an original dataset announced via ProteomeXchange.

Title	System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel SUMO target proteins and acceptor lysines relevant for genome stability
Description	Genotoxic agents can cause replication fork stalling in dividing cells due to DNA lesions, eventually leading to replication fork collapse when the damage is not repaired. Small Ubiquitin-like Modifiers (SUMOs) are known to counteract replication stress, nevertheless, only a small number of relevant SUMO target proteins are known. To address this, we have purified and identified SUMO-2 target proteins regulated by replication stress in human cells. The developed methodology enabled single step purification of His10-SUMO-2 conjugates under denaturing conditions with high yield and high purity. The methodology is generic and is widely applicable in the ubiquitin field. Following statistical analysis on five biological replicates, a total of 566 SUMO-2 targets were identified. After 2 hours of Hydroxyurea treatment, 10 proteins were up-regulated for SUMOylation and 2 proteins were down-regulated for SUMOylation, whereas after 24 hours, 35 proteins were up-regulated for SUMOylation and 13 proteins were down-regulated for SUMOylation. A site-specific approach was used to map over 1,000 SUMO-2 acceptor lysines in target proteins. A large subset of these identified proteins function in one network that consists of interacting replication factors, transcriptional regulators, DNA damage response factors including MDC1, ATR-interacting protein ATRIP, the Bloom syndrome protein and the BLM-binding partner RMI1, the crossover junction endonuclease EME1, BRCA1 and CHAF1A. Furthermore, centromeric proteins and signal transducers were dynamically regulated by SUMOylation upon replication stress. Our results uncover a comprehensive network of SUMO target proteins dealing with replication damage and provide a framework for detailed understanding of the role of SUMOylation to counteract replication stress. Ultimately, our study reveals how a post-translational modification is able to orchestrate a large variety of different proteins to integrate different nuclear processes with the aim of dealing with the induced DNA damage
HostingRepository	PRIDE
AnnounceDate	2015-03-12
AnnouncementXML	Submission_2015-03-12_08:26:16.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jer-gung Chang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; sumoylated lysine
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-01-27 01:37:54	ID requested
⏵ 1	2015-03-12 08:26:17	announced

Xiao Z, Chang JG, Hendriks IA, Sigur, ð, sson JO, Olsen JV, Vertegaal AC, System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability. Mol Cell Proteomics, 14(5):1419-34(2015) [pubmed]

curator keyword: Biological

submitter keyword: DNA damage, Affinity purification, Label free quantification

Alfred Vertegaal
contact affiliation	Leiden University Medical Center Molecular Cell Biology group
contact email	A.C.O.Vertegaal@lumc.nl
lab head
Jer-gung Chang
contact affiliation	LUMC
contact email	j.g.chang@lumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001736
     1. Label: PRIDE project
     2. Name: System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel SUMO target proteins and acceptor lysines relevant for genome stability