ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones.
Budding yeast Mec1, homolog of mammalian ATR, is an essential protein that mediates S-phase checkpoint responses and meiotic recombination. Elimination of Mec1 function leads to genomewide fork stalling followed by chromosome breakage. Breaks do not result from stochastic collapse of stalled forks or other incidental lesions; instead, they occur in specific regions of the genome during a G2 chromosomal transition. Break regions are found to be genetically encoded replication slow zones (RSZs), a newly discovered yeast chromosomal determinant. Thus, Mec1 has important functions in normal S phase and the genome instability of mec1 (and, analogously, ATR-/-) mutants stems from defects in these basic roles.
Cha
Rita S
RS
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Kleckner
Nancy
N
D019457:Chromosome Breakage; D015825:Chromosomes, Fungal / Q000502:physiology*; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000502:physiology*; D016193:G1 Phase; D016195:G2 Phase; D016681:Genome, Fungal; D006918:Hydroxyurea / Q000494:pharmacology; D007399:Interphase; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins
D004271:DNA, Fungal; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D006918:Hydroxyurea