rad3atr decorates critical chromosomal domains with γh2a to protect genome integrity during s-phase in fission yeastrad3atr装饰至关重要的染色体与γh2a域保护基因组完整性在裂殖酵母s阶段.pdfVIP

Rad3ATR Decorates Critical Chromosomal Domains with cH2A to Protect Genome Integrity during S-Phase in Fission Yeast 1 ´ ´ 1 2 3 3 Sophie Rozenzhak , Eva Mejıa-Ramırez , Jessica S. Williams , Lana Schaffer , Jennifer A. Hammond , Steven R. Head3, Paul Russell 1,4* 1 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America, 2 Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America, 3 DNA Array Core Facility, The Scripps Research Institute, La Jolla, California, United States of America, 4 Department of Cell Biology, The Scripps Research Institute, La Jolla, California, United States of America Abstract Schizosaccharomyces pombe Rad3 checkpoint kinase and its human ortholog ATR are essential for maintaining genome integrity in cells treated with genotoxins that damage DNA or arrest replication forks. Rad3 and ATR also function during unperturbed growth, although the events triggering their activation and their critical functions are largely unknown. Here, we use ChIP-on-chip analysis to map genomic loci decorated by phosphorylated histone H2A (cH2A), a Rad3 substrate that establishes a chromatin-based recruitment platform for Crb2 and Brc1 DNA repair/checkpoint proteins. Unexpectedly, cH2A marks a diverse array of genomic features during S-phase, including natural replication fork barriers and a fork breakage site, retrotransposons, heterochromatin in the centromeres and telomeres, and ribosomal RNA (rDNA) repeats. cH2A formation at the centromeres and