Dataset Information

TRF1 averts chromatin remodelling, recombination and replication dependent-Break Induced Replication at mouse telomeres

ABSTRACT: Telomeric repeat sequences are prone to induce replication stress and one of the core telomere binding proteins, TRF1, is thought to counteract these problems. The molecular mechanisms coming into play upon TRF1 loss were not clearly defined though. This study combines an inducible TRF1 loss with telomere-targeted proteomics to analyze the incurring changes. The results show that loss of TRF1 causes important alterations in telomere associated proteins and the new profile resembles in a number of ways that of cells in which telomeres are maintained by telomerase-independent mechanisms, named ALT. The presence of DNA repair proteins (MRN complex, the SMC5/6 complex), some increases in telomere colocalization with PML bodies, sister chromatid exchanges and clear signs of increased TERRA transcription and mitotic break-induced replication are part of these phenotypes. The data also show that these early ALT phenotypes can be differentiated from drug induced replication stress, and part of this ALT response is conserved in human cells. These studies therefore point to a critical role for TRF1 in preventing the emergence of ALT and hence immortalization of cells. Given that the details for how ALT actually is initiated remained unclear, these findings are an important step forward and will spur new research into that question.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Fibroblast

SUBMITTER: Alex Montoya

LAB HEAD: Jean-Baptiste Vannier

PROVIDER: PXD017022 | Pride | 2020-01-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MaxQuant_txt_p007.zip	Other
	MaxQuant_txt_p009.zip	Other
	Uniprot_Mouse_20160627.fasta	Fasta
	b025p007_L1_1A_rep1.raw	Raw
	b025p007_L1_1A_rep2.raw	Raw

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Publications

TRF1 averts chromatin remodelling, recombination and replication dependent-break induced replication at mouse telomeres.

Porreca Rosa Maria RM Herrera-Moyano Emilia E Skourti Eleni E Law Pui Pik PP Gonzalez Franco Roser R Montoya Alex A Faull Peter P Kramer Holger H Vannier Jean-Baptiste JB

eLife 20200114

Telomeres are a significant challenge to DNA replication and are prone to replication stress and telomere fragility. The shelterin component TRF1 facilitates telomere replication but the molecular mechanism remains uncertain. By interrogating the proteomic composition of telomeres, we show that mouse telomeres lacking TRF1 undergo protein composition reorganisation associated with the recruitment of DNA damage response and chromatin remodellers. Surprisingly, mTRF1 suppresses the accumulation of ...[more]

PMID: 31934863

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