Rif1 and Exo1 regulate the genomic instability following telomere losses.pdf (1.18 MB)
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Rif1 and Exo1 regulate the genomic instability following telomere losses

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journal contribution
posted on 05.10.2016, 10:57 by Yuan Xue, Marcus E Marvin, Iglika G. Ivanova, David Lydall, Edward J. Louis, Laura Maringele
Telomere attrition is linked to cancer, diabetes, cardiovascular disease and aging. This is because telomere losses trigger further genomic modifications, culminating with loss of cell function and malignant transformation. However, factors regulating the transition from cells with short telomeres, to cells with profoundly altered genomes, are little understood. Here, we use budding yeast engineered to lack telomerase and other forms of telomere maintenance, to screen for such factors. We show that initially, different DNA damage checkpoint proteins act together with Exo1 and Mre11 nucleases, to inhibit proliferation of cells undergoing telomere attrition. However, this situation changes when survivors lacking telomeres emerge. Intriguingly, checkpoint pathways become tolerant to loss of telomeres in survivors, yet still alert to new DNA damage. We show that Rif1 is responsible for the checkpoint tolerance and proliferation of these survivors, and that is also important for proliferation of cells with a broken chromosome. In contrast, Exo1 drives extensive genomic modifications in survivors. Thus, the conserved proteins Rif1 and Exo1 are critical for survival and evolution of cells with lost telomeres.

History

Citation

Aging Cell, 2016, 15 (3), pp. 553-562

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Department of Genetics

Version

VoR (Version of Record)

Published in

Aging Cell

Publisher

Wiley for Anatomical Society of Great Britain and Ireland

issn

1474-9718

eissn

1474-9726

Acceptance date

17/02/2016

Copyright date

2016

Available date

05/10/2016

Publisher version

http://onlinelibrary.wiley.com/doi/10.1111/acel.12466/abstract;jsessionid=B6B0BC5E8AD83D9609657515A46E0744.f03t03

Language

en

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