Author: Xie Z1, Jay KA2, Smith DL2, Zhang Y1, Liu Z1, Zheng J3, Tian R4, Li H5, Blackburn EH6.
Affiliation: 1Center for Quantitative Biology, School of Physics and The Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. 2Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. 3Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. 4Center for Quantitative Biology, School of Physics and The Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. 5Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: haoli@genome.ucsf.edu. 6Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: elizabeth.blackburn@ucsf.edu.
Conference/Journal: Cell.
Date published: 2015 Feb 26
Other:
Volume ID: 160 , Issue ID: 5 , Pages: 928-39 , Special Notes: doi: 10.1016/j.cell.2015.02.002 , Word Count: 145
Abstract
Telomerase is required for long-term telomere maintenance and protection. Using single budding yeast mother cell analyses we found that, even early after telomerase inactivation (ETI), yeast mother cells show transient DNA damage response (DDR) episodes, stochastically altered cell-cycle dynamics, and accelerated mother cell aging. The acceleration of ETI mother cell aging was not explained by increased reactive oxygen species (ROS), Sir protein perturbation, or deprotected telomeres. ETI phenotypes occurred well before the population senescence caused late after telomerase inactivation (LTI). They were morphologically distinct from LTI senescence, were genetically uncoupled from telomere length, and were rescued by elevating dNTP pools. Our combined genetic and single-cell analyses show that, well before critical telomere shortening, telomerase is continuously required to respond to transient DNA replication stress in mother cells and that a lack of telomerase accelerates otherwise normal aging.
Copyright © 2015 Elsevier Inc. All rights reserved.
PMID: 25723167