At Short Telomeres Tel1 Directs Early Replication and Phosphorylates Rif1

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The ends of chromosomes are protected by specialized structures called telomeres, which prevent their recognition as DNA breaks and enable recruitment of telomerase, the reverse transcriptase that maintains telomere length by replacing terminal TG-repeat sequences lost during successive rounds of DNA replication. Chromosomal DNA is replicated from initiation sites called origins, which are activated in a reproducible temporal sequence. Replication origins close to telomeres are subject to specialized temporal control that contributes to telomere stabilization: origins close to normal-length telomeres initiate replication late, while those close to shortened telomeres initiate early. Here we uncover the control mechanism that links telomere length with replication timing. Rif1, one of the components of telomeric chromatin, directs late replication of normal telomeres by delaying the activation of nearby origins. Our experiments show that a kinase called Tel1, which is recruited to shortened telomeres, neutralizes the origin-delaying activity of Rif1. We also find that Tel1 phosphorylates Rif1 at short telomeres, although our investigation shows this phosphorylation is not the sole mechanism through which Tel1 prevents Rif1-mediated replication delay. Since correct telomere replication timing control is important for telomerase-mediated length maintenance, this discovery represents an important step towards understanding the molecular mechanisms that ensure proper long-term stabilization of chromosome ends, as well as the controls over the DNA replication temporal program.

Vyšlo v časopise: At Short Telomeres Tel1 Directs Early Replication and Phosphorylates Rif1. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004691
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004691

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