Hiding at the ends of yeast chromosomes: telomeres, nucleases and checkpoint pathways.
Telomeres stabilise DNA at the ends of chromosomes, preventing chromosome fusion and genetic instability. Telomeres differ from double strand breaks in that they activate neither DNA repair nor DNA damage checkpoint pathways. Paradoxically DNA repair and checkpoint genes play critical roles in telomere stability. Recent work has provided insights into the roles of DNA repair and DNA damage checkpoint pathways in the physiological maintenance of telomeres and in cellular responses when telomeres become uncapped. In budding yeast the Mre11p nuclease, along with other unidentified nucleases, plays critical roles in physiological telomere maintenance. However, when telomeres are uncapped, the 5'-to-3' exonuclease, Exo1p, plays a critical role in generating single-stranded DNA and activating checkpoint pathways. Intriguingly Exo1p does not play an important role in normal telomere maintenance. Although checkpoint pathways are not normally activated by telomeres, at least four different types of telomere defect activate checkpoint pathways. Interestingly, each of these telomere defects depends on a different subset of checkpoint proteins to induce cell cycle arrest. A model for how a spectrum of telomeric states might interact with telomerase and checkpoint pathways is proposed.
Lydall
David
D
School of Biological Sciences, University of Manchester, G38 Stopford Building, Oxford Road, Manchester M13 9PT, UK. lydall@man.ac.uk
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication / Q000502:physiology; D003851:Deoxyribonucleases / Q000378:metabolism*; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004790:Enzyme Induction; D005090:Exodeoxyribonucleases / Q000378:metabolism; D008958:Models, Molecular; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D004718:Saccharomycetales / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; C028450:exodeoxyribonuclease I