PXD015453-2

PXD015453 is an original dataset announced via ProteomeXchange.

Title	CDK13 cooperates with CDK12 to control global RNA polymerase II processivity
Description	The RNA polymerase II (POLII) driven transcription cycle is tightly regulated at distinct checkpoints through cyclin dependent kinases (CDKs) and their cognate Cyclins. The molecular events underpinning transcriptional elongation and processivity and CDK-Cyclins involved remain poorly understood. Using CRISPR-CAS9 homology-directed-repair we generated analog-sensitive-kinase variants of CDK12 and CDK13 to probe their individual and shared biological and molecular roles. Single inhibition of CDK12 or CDK13 induced transcriptional responses associated with DNA-damage and cellular growth signaling pathways respectively, with minimal effects on cell viability. In contrast, dual-kinase inhibition potently induced cell death, which was associated with extensive genome-wide transcriptional changes including wide-spread use of alternative 3’ polyadenylation sites. At the molecular level dual-kinase inhibition resulted in the loss of POLII CTD phosphorylation and greatly reduced POLII elongation rates and processivity. These data define significant redundancy between CDK12 and CDK13, and identify both as fundamental regulators of global POLII processivity and transcription elongation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:02:54.546.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jarrod Sandow
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-16 01:10:49	ID requested
1	2020-04-29 22:22:32	announced
⏵ 2	2024-10-22 05:02:54	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: CDK13,CDK12, phosphoproteomics, polymerase

Ricky Johnstone
contact affiliation	Executive Director Cancer Research, Peter MacCallum Cancer Centre
contact email	ricky.johnstone@petermac.org
lab head
Jarrod Sandow
contact affiliation	WEHI
contact email	sandow@wehi.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015453
     1. Label: PRIDE project
     2. Name: CDK13 cooperates with CDK12 to control global RNA polymerase II processivity