The PAL-Mechanism of Chromosome Maintenance: Causes and Consequences

Abstract

It is generally accepted that cells with extensive, un-repaired DNA damage canescape cell cycle arrest only by disabling checkpoint pathways and they usuallyperish, after several divisions, presumably due to catastrophic events on theirchromosomes. Our recently discovered PAL-mechanism opens a new perspective,that some eukaryotic cells with short chromosome ends (telomeres), usually detectedas DNA damage, can escape permanent cell cycle arrest (senescence) under specialconditions, despite having intact checkpoints and even immortalize, despite lackingtelomerase or other telomere-elongation mechanisms. Here we present the firstevidence that telomerase-lacking, senescent cells generate DNA damage (singlestranded DNA) at internal chromosomal regions, while the telomere proximal singlestranded DNA appears to be either lost or repaired. This first evidence is from thebudding yeast model system. We also discuss the possible involvement of the PALmechanismin carcinogenesis.