PXD044310-1

PXD044310 is an original dataset announced via ProteomeXchange.

Title	Interactome analysis of elongating RNAPII after induction of DNA damage by IP-MS/MS
Description	Endogenous aldehydes induce inter-strand crosslinks (ICL) and DNA-protein crosslinks (DPC). While DNA-repair and aldehyde-clearance systems cope with cellular toxicity, deficiencies in these mechanisms cause genome-instability disorders. The FA-pathway, defective in Fanconi anemia (FA), specifically removes ICL. In contrast, SPRTN, compromised in Ruijs-Aalfs syndrome, eliminates DPC during replication. However, AMeDS patients lacking aldehyde-detoxification display combined features of FA and Cockayne syndrome, associated with transcription-coupled repair (TCR) deficiency, suggesting a novel repair mechanism for aldehyde-induced DNA lesions in active genes. In this report, we demonstrate efficient resolution of aldehyde-induced transcription-blocking lesions by TCR. Mass-spectrometry and DPC-seq identify the TCR complex and additional factors involved in DPC removal and formaldehyde-induced damage tolerance. Notably, TFIIS-dependent cleavage of stalled-RNAPII transcripts exclusively protects against formaldehyde-induced damage. A mouse-model lacking both aldehyde-clearance and TCR pathways confirms endogenous DPC accumulation in transcribed regions. These findings highlight the importance of DPC removal in preventing transcription-roadblocks and contribute to understanding disorders related to aldehyde clearance and TCR deficiencies.
HostingRepository	PRIDE
AnnounceDate	2024-02-12
AnnouncementXML	Submission_2024-02-11_17:11:43.230.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yasuyoshi Oka
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-02 21:48:09	ID requested
⏵ 1	2024-02-11 17:11:43	announced
2	2024-10-22 06:29:04	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human HeLa cells IP-MS/MS RNAPII DNA damage

Tomoo Ogi
contact affiliation	Department of Genetics, Research Institute of Environmental Medicine (RIEM), Nagoya University
contact email	togi@riem.nagoya-u.ac.jp
lab head
Yasuyoshi Oka
contact affiliation	Department of Genetics, Research Institute of Environmental Medicine (RIEM), Nagoya University
contact email	yasuyoshi.oka@riem.nagoya-u.ac.jp
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044310
     1. Label: PRIDE project
     2. Name: Interactome analysis of elongating RNAPII after induction of DNA damage by IP-MS/MS