Recombination machinery compensates telomere loss in the absence of telomerase.

Recombination machinery compensates telomere loss in the absence of telomerase.

The chromosomes of most eukaryotic species are linear, consisting of a single DNA double-helix running from one end to the other. Each chromosome thus has two ends and these are protected by specialized DNA-protein structures named telomeres. The importance of telomere structure is readily observed in the severe genetic instability and cell death that result from its absence.

In its last study ( Olivier et al., 2018), the team of Charles White and Maria Gallego unveiled mechanisms by which recombination machinery contributes to protect the telomeres from replicative failure, ensuring  their stability.

Telomeres are shortened at each cell division due to the inability of the DNA replication machinery to fully copy linear DNA molecules, and this replicative erosion, together with the dramatic consequences of telomere loss, creates a "molecular clock" which limits the number of times a cell can divide - creating a major barrier against cancer in animals (https://www.nobelprize.org/nobel_prizes/medicine/laureates/2009/illpres.html). In contrast to all other regions of the genome, the placement of telomeres at the ends of the chromosomes means that collapse of a telomeric replication fork cannot be rescued by the arrival of a second fork coming in the other direction - making telomeres particularly sensitive to faults in the DNA replication process. A fatal outcome of such events can however be avoided by the repair of the shortened chromosome end via activation of the telomerase or genetic recombination with an intact telomere and this is the subject of the research published in this article.

Through a combination of genetic, molecular and cytological approaches, we show in this article the presence of a key recombination protein (RAD51) at eroding telomeres and demonstrate the importance of its role in compensating DNA replication stress. This work also brings to light an unexpected role for the DNA helicase RTEL1 in these events and furthers our understanding of the molecular mechanisms of recombination and DNA replication ensuring telomere stability and the maintenance of genome integrity.

This study has been published in Nucleic Acid Researchs ( Olivier et al., 2018).

Last modified: 08/03/2018