PMID- 23307868 OWN - NLM STAT- MEDLINE DCOM- 20130226 LR - 20211203 IS - 1549-5477 (Electronic) IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 27 IP - 1 DP - 2013 Jan 1 TI - ATR-like kinase Mec1 facilitates both chromatin accessibility at DNA replication forks and replication fork progression during replication stress. PG - 74-86 LID - 10.1101/gad.202978.112 [doi] AB - 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. FAU - Rodriguez, Jairo AU - Rodriguez J AD - Fred Hutchinson Cancer Research Center, Division of Basic Sciences, Seattle, Washington 98109, USA. FAU - Tsukiyama, Toshio AU - Tsukiyama T LA - eng GR - R01 GM078259/GM/NIGMS NIH HHS/United States GR - R01 GM058465/GM/NIGMS NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States GR - GM078259/GM/NIGMS NIH HHS/United States GR - GM058465/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (Chromatin) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Nucleosomes) RN - 0 (Saccharomyces cerevisiae Proteins) RN - EC 2.7.11.1 (MEC1 protein, S cerevisiae) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 3.1.31.1 (Micrococcal Nuclease) SB - IM MH - Chromatin/chemistry/*metabolism MH - Chromosome Mapping MH - *DNA Replication MH - Genome/genetics MH - Intracellular Signaling Peptides and Proteins/genetics/*metabolism MH - Micrococcal Nuclease/metabolism MH - Mutation/genetics MH - Nucleosomes/metabolism MH - Protein Serine-Threonine Kinases/genetics/*metabolism MH - S Phase/genetics MH - Saccharomyces cerevisiae/*enzymology/*genetics MH - Saccharomyces cerevisiae Proteins/genetics/*metabolism MH - Stress, Physiological PMC - PMC3553285 EDAT- 2013/01/12 06:00 MHDA- 2013/02/27 06:00 PMCR- 2013/07/01 CRDT- 2013/01/12 06:00 PHST- 2013/01/12 06:00 [entrez] PHST- 2013/01/12 06:00 [pubmed] PHST- 2013/02/27 06:00 [medline] PHST- 2013/07/01 00:00 [pmc-release] AID - 27/1/74 [pii] AID - 10.1101/gad.202978.112 [doi] PST - ppublish SO - Genes Dev. 2013 Jan 1;27(1):74-86. doi: 10.1101/gad.202978.112.