Life and Death without Telomerase: The Model.

, a model organism in telomere biology, has been instrumental in pioneering a comprehensive understanding of the molecular processes that occur in the absence of telomerase across eukaryotes. This exploration spans investigations into telomere dynamics, intracellular signaling cascades, and organelle-mediated responses, elucidating their impact on proliferative capacity, genome stability, and cellular variability. Through the lens of budding yeast, numerous sources of cellular heterogeneity have been identified, dissected, and modeled, shedding light on the risks associated with telomeric state transitions, including the evasion of senescence.

Hog1 acts in a Mec1-independent manner to counteract oxidative stress following telomerase inactivation in Saccharomyces cerevisiae.

Replicative senescence is triggered when telomeres reach critically short length and activate permanent DNA damage checkpoint-dependent cell cycle arrest. Mitochondrial dysfunction and increase in oxidative stress are both features of replicative senescence in mammalian cells. However, how reactive oxygen species levels are controlled during senescence is elusive.

TERRA and Telomere Maintenance in the Yeast .

Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally silent regions because of their constitutive heterochromatin signature until telomeric long non-coding RNAs (LncRNAs) were discovered.

A noncanonical response to replication stress protects genome stability through ROS production, in an adaptive manner.

Cells are inevitably challenged by low-level/endogenous stresses that do not arrest DNA replication. Here, in human primary cells, we discovered and characterized a noncanonical cellular response that is specific to nonblocking replication stress. Although this response generates reactive oxygen species (ROS), it induces a program that prevents the accumulation of premutagenic 8-oxoguanine in an adaptive way.

Lamin B1 sequesters 53BP1 to control its recruitment to DNA damage.

Double-strand breaks (DSBs) are harmful lesions and a major cause of genome instability. Studies have suggested a link between the nuclear envelope and the DNA damage response. Here, we show that lamin B1, a major component of the nuclear envelope, interacts directly with 53BP1 protein, which plays a pivotal role in the DSB repair.