PXD014843

PXD014843 is an original dataset announced via ProteomeXchange.

Title	A cell cycle switch in TRF2 controls t-loop dynamics and DNA secondary structure resolution across the genome
Description	Telomere end-protection by the shelterin complex prevents DNA damage signalling and promiscuous repair at chromosome ends. Evidence suggests that the 3’ single-stranded telomere end can assemble into a lasso-like t-loop configuration, which has been proposed to safeguard chromosome ends from being recognized as DNA double strand breaks. Mechanisms must also exist to transiently disassemble t-loops to allow faithful telomere replication and to permit telomerase access to the 3’-end to solve the end replication problem. However, the regulation and physiological importance of t-loops in end-protection remains uncertain. Here, we identify a CDK phosphorylation site in the shelterin subunit, TRF2 (Ser365), whose dephosphorylation in S-phase by the PP6C/R3 phosphatase provides a narrow window during which the helicase RTEL1 is able to transiently access and unwind t-loops to facilitate telomere replication. Re-phosphorylation of TRF2 on Ser365 outside of S-phase is required to release RTEL1 from telomeres, which not only protects t-loops from promiscuous unwinding and inappropriate ATM activation, but also counteracts replication conflicts at DNA secondary structures arising within telomeres and across the genome. Hence, a phospho-switch in TRF2 coordinates assembly and disassembly of t-loops during the cell cycle, which protects telomeres from replication stress and an unscheduled DNA damage response.
HostingRepository	PRIDE
AnnounceDate	2019-11-25
AnnouncementXML	Submission_2019-11-25_02:53:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Helen Flynn
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-31 01:23:28	ID requested
⏵ 1	2019-11-25 02:53:17	announced

Sarek G, Kotsantis P, Ruis P, Van Ly D, Margalef P, Borel V, Zheng XF, Flynn HR, Snijders AP, Chowdhury D, Cesare AJ, Boulton SJ, CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle. Nature, 575(7783):523-527(2019) [pubmed]

submitter keyword: telomeres, t-loops, shelterin, DNA repair, DNA replication, genome stability, cell cycle, TRF2, CDK, phosphatases, RTEL1, LC-MS/MS

Bram Snijders
contact affiliation	Mass Spectrometry Proteomics Science Technology Platform The Francis Crick Institute
contact email	bram.snijders@crick.ac.uk
lab head
Helen Flynn
contact affiliation	The Francis Crick Institute
contact email	helen.flynn@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014843
     1. Label: PRIDE project
     2. Name: A cell cycle switch in TRF2 controls t-loop dynamics and DNA secondary structure resolution across the genome