Essential roles of Xenopus TRF2 in telomere end protection and replication
- 10 May 2011
- journal article
- Published by Wiley in Genes to Cells
- Vol. 16 (6), 728-739
- https://doi.org/10.1111/j.1365-2443.2011.01520.x
Abstract
TRF1 and TRF2 are double-stranded (ds) telomere DNA-binding proteins and the core members of shelterin, a complex that provides the structural and functional basis of telomere functions. We have reported that unlike mammalian TRF1 that constitutively binds to chromatin, Xenopus TRF1 (xTRF1) associates with mitotic chromatin but dissociates from interphase chromatin reconstituted in Xenopus egg extracts. This finding raised the possibility that xTRF1 and Xenopus TRF2 (xTRF2) contribute to telomere functions in a manner different from mammalian TRF1 and TRF2. Here, we focused on the role of xTRF2. We prepared chromatin reconstituted in egg extracts immunodepleted for xTRF2. Compared to mock-depleted nuclei, DNA damage response at telomeres was activated, and bulk DNAs were poorly replicated in xTRF2-depleted nuclei. The replication defect was rescued by inactivating ATR through the addition of anti-ATR neutralizing antibody, suggesting that ATR plays a role in the defect. Interestingly, the bulk DNA replication defect, but not the DNA damage response at telomeres, was rescued by supplementing the xTRF2-depleted extracts with recombinant xTRF2 (rTRF2). We propose that xTRF2 is required for both efficient replication of bulk DNA and protection from the activation of the DNA damage checkpoints pathway, and that those two functions are mechanistically separableKeywords
This publication has 32 references indexed in Scilit:
- A Shared Docking Motif in TRF1 and TRF2 Used for Differential Recruitment of Telomeric ProteinsScience, 2008
- Chromosome Fragile SitesAnnual Review of Genetics, 2007
- Disappearance of the Telomere Dysfunction-Induced Stress Response in Fully Senescent CellsCancer Research, 2004
- Vertebrate tankyrase domain structure and sterile alpha motif (SAM)-mediated multimerizationBiochemical Journal, 2003
- Cell cycle checkpoint signaling through the ATM and ATR kinasesGenes & Development, 2001
- The Xenopus Chromokinesin Xkid Is Essential for Metaphase Chromosome Alignment and Must Be Degraded to Allow Anaphase Chromosome MovementCell, 2000
- Regulated Formation of Extrachromosomal Circular DNA Molecules during Development in Xenopus laevisMolecular and Cellular Biology, 1999
- Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factorThe Journal of cell biology, 1993
- Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro: Studies in XenopusCell, 1990
- Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggsCell, 1986