PXD017931

PXD017931 is an original dataset announced via ProteomeXchange.

Title	Integrative Structural Model of DNA-PK Synapsis
Description	In non-homologous end joining repair of DNA double strand breaks, DNA dependent protein kinase catalytic subunit (DNA-PKcs) and Ku70/80 binds the free DNA ends forming the holoenzyme DNA-PK. DNA-PK synapses across the break to tether the broken ends in the initial long range synaptic complex. We generated an integrative structural model of DNA-PK synapsis at a precision of 13.5Å with crosslinking mass spectrometry (XL-MS) restraints. While our hydrogen deuterium exchange (HX) analysis revealed an allosteric axis in DNA-PK connecting DNA binding (including the plug domain) to the kinase domain. Our model presents a symmetrical synapsis primarily through head to head interactions and protection of the DNA by previously uncharacterized a plug domain. The offset of the DNA in our model allows access to downstream processing enzymes, while the combination of DNA binding and kinase loading creates a tensed state that could have roles in the re-arrangement/dissociation of DNA-PKcs as the repair process progresses.
HostingRepository	PRIDE
AnnounceDate	2021-01-20
AnnouncementXML	Submission_2021-01-19_22:00:00.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Morgan Hepburn
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-09 01:28:14	ID requested
⏵ 1	2021-01-19 22:00:01	announced

Hepburn M, Saltzberg DJ, Lee L, Fang S, Atkinson C, Strynadka NCJ, Sali A, Lees-Miller SP, Schriemer DC, The active DNA-PK holoenzyme occupies a tensed state in a staggered synaptic complex. Structure, 29(5):467-478.e6(2021) [pubmed]

submitter keyword: Hydrogen deuterium exchange, crosslinking, DNA-PK

David C. Schriemer
contact affiliation	Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary Department of Chemistry, University of Calgary
contact email	dschriem@ucalgary.ca
lab head
Morgan Hepburn
contact affiliation	University of Calgary
contact email	mhoeppne@ucalgary.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017931
     1. Label: PRIDE project
     2. Name: Integrative Structural Model of DNA-PK Synapsis