Break-Induced Replication Requires DNA Damage-Induced Phosphorylation of Pif1 and Leads to Telomere Lengthening

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Telomeres are the ends of linear eukaryotic chromosomes maintained by an enzyme called telomerase. Non-telomeric DNA ends are often generated as a result of broken replication forks and are usually repaired by break-induced replication (BIR) or homologous recombination to avoid genomic instability. However, telomerase can interfere with the repair by adding a new telomere to a broken DNA end, or the break can be ligated to a telomere, thereby inducing genome re-arrangements that are often found in human genetic disorders and cancer. To understand how cells avoid erroneous repair, we studied cdc9-1 yeast mutant cells that generate broken replication forks with high frequency. We discovered that, in cells with DNA damage, a helicase called Pif1 is phosphorylated and this phosphorylation enables Pif1 not only to inhibit telomerase at broken DNA ends but also stimulate the break repair by BIR, which in turn leads to additional telomere lengthening. Thus, a new regulatory pathway stimulates accurate break repair by BIR and at the same time promotes telomerase activity at telomeres.

Vyšlo v časopise: Break-Induced Replication Requires DNA Damage-Induced Phosphorylation of Pif1 and Leads to Telomere Lengthening. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004679
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004679

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