TRF1 averts chromatin remodelling, recombination and replication dependent-break induced replication at mouse telomeres.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31934863.
- Also identified by DOI 10.7554/eLife.49817 and PMC identifier 6986873.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 promyelocytic leukemia (PML) protein, BRCA1 and the SMC5/6 complex at telomeres, which is associated with increased Homologous Recombination (HR) and TERRA transcription. We uncovered a previously unappreciated role for mTRF1 in the suppression of telomere recombination, dependent on SMC5 and also POLD3 dependent Break Induced Replication at telomeres. We propose that TRF1 facilitates S-phase telomeric DNA synthesis to prevent illegitimate mitotic DNA recombination and chromatin rearrangement.
Medical subject headings
- Chromatin Assembly and Disassembly
- DNA Breaks
- DNA Replication
- Recombination, Genetic
- Telomere
- Telomeric Repeat Binding Protein 1