Dataset Information

A cell cycle switch in TRF2 controls t-loop dynamics and DNA secondary structure resolution across the genome

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Helen Flynn

LAB HEAD: Bram Snijders

PROVIDER: PXD014843 | Pride | 2019-11-25

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	DRS6824A10RW3_GS_B2DRS6824A10RW3-40-508591.raw	Raw
	DRS6824A11RW3_GS_C2DRS6824A11RW3-40-508589.raw	Raw
	DRS6824A12RW3_GS_D2DRS6824A12RW3-40-508587.raw	Raw
	DRS6824A13RW3_GS_E2DRS6824A13RW3-40-508585.raw	Raw
	DRS6824A14RW3_GS_F2DRS6824A14RW3-40-508583.raw	Raw

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Publications

CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle.

Sarek Grzegorz G Kotsantis Panagiotis P Ruis Phil P Van Ly David D Margalef Pol P Borel Valerie V Zheng Xiao-Feng XF Flynn Helen R HR Snijders Ambrosius P AP Chowdhury Dipanjan D Cesare Anthony J AJ Boulton Simon J SJ

Nature 20191113 7783

The protection of telomere ends 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<sup>1,2</sup>, which has been proposed to safeguard chromosome ends from being recognized as DNA double-strand breaks<sup>2</sup>. Mechanisms must also exist to transiently disassemble t-loops to allow accurate telomere replication and to permit telomerase a ...[more]

PMID: 31723267

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