title: ATR-like kinase Mec1 facilitates both chromatin accessibility at DNA replication forks and replication fork progression during replication stress.
abstract: Faithful DNA replication is essential for normal cell division and differentiation. In eukaryotic cells, DNA replication takes place on chromatin. This poses the critical question as to how DNA replication can progress through chromatin, which is inhibitory to all DNA-dependent processes. Here, we developed a novel genome-wide method to measure chromatin accessibility to micrococcal nuclease (MNase) that is normalized for nucleosome density, the NCAM (normalized chromatin accessibility to MNase) assay. This method enabled us to discover that chromatin accessibility increases specifically at and ahead of DNA replication forks in normal S phase and during replication stress. We further found that Mec1, a key regulatory ATR-like kinase in the S-phase checkpoint, is required for both normal chromatin accessibility around replication forks and replication fork rate during replication stress, revealing novel functions for the kinase in replication stress response. These results suggest a possibility that Mec1 may facilitate DNA replication fork progression during replication stress by increasing chromatin accessibility around replication forks.
authors: Fred Hutchinson Cancer Research Center, Division of Basic Sciences, Seattle, Washington 98109, USA.
authors: Jairo
authors: J
authors: Rodriguez
authors: Toshio
authors: T
authors: Tsukiyama
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D002874:Chromosome Mapping; D004261:DNA Replication; D016678:Genome / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008836:Micrococcal Nuclease / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009707:Nucleosomes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D002843:Chromatin; D047908:Intracellular Signaling Peptides and Proteins; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D008836:Micrococcal Nuclease