1. Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.
- Author
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Mendez-Bermudez A, Lototska L, Bauwens S, Giraud-Panis MJ, Croce O, Jamet K, Irizar A, Mowinckel M, Koundrioukoff S, Nottet N, Almouzni G, Teulade-Fichou MP, Schertzer M, Perderiset M, Londoño-Vallejo A, Debatisse M, Gilson E, and Ye J
- Subjects
- Cell Line, Tumor, Centromere genetics, Chromatin genetics, DNA Helicases genetics, G-Quadruplexes, HeLa Cells, Humans, S Phase genetics, DNA Replication genetics, Genome genetics, Heterochromatin genetics, Telomere genetics, Telomeric Repeat Binding Protein 2 genetics
- Abstract
Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin. In a process involving its N-terminal basic domain, TRF2 binds to pericentromeric Satellite III sequences during S phase, allowing the recruitment of the G-quadruplex-resolving helicase RTEL1 to facilitate fork progression. We also show that TRF2 is required for the stability of other heterochromatic regions localized throughout the genome, paving the way for future research on heterochromatic replication and its relationship with aging and cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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