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The Arabidopsis ATRIP ortholog is required for a programmed response to replication inhibitors
Author(s) -
Sweeney Paul R.,
Britt Anne B.,
Culligan Kevin M.
Publication year - 2009
Publication title -
the plant journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.058
H-Index - 269
eISSN - 1365-313X
pISSN - 0960-7412
DOI - 10.1111/j.1365-313x.2009.03975.x
Subject(s) - dna damage , biology , aphidicolin , dna replication , arabidopsis , dna repair , mutant , replication protein a , control of chromosome duplication , eukaryotic dna replication , replication factor c , dna replication factor cdt1 , microbiology and biotechnology , genetics , gene , dna , dna binding protein , transcription factor
Summary The programmed response to replication inhibitors in eukaryotic cells requires the protein kinase ATR (ataxia telangiectasia mutated and rad3‐related), which is activated primarily through the persistence of replication protein A (RPA)‐bound single‐stranded DNA at stalled replication forks and sites of DNA damage undergoing excision repair. Once activated, ATR initiates a cascade of events, including cell‐cycle arrest and induction of DNA repair, to mitigate the mutagenic effects of DNA replication in the presence of damage and/or blockage. While many of the molecular regulators of ATR have been determined in yeast and animal cells, little is known about ATR regulation in plants. To genetically define ATR regulatory pathways in Arabidopsis, we describe here a genetic screen for identifying mutants that display a characteristic phenotype of Arabidopsis atr null mutants – hypersensitivity to the replication blocking agent hydroxyurea (HU). Employing this screen, we isolated a novel mutant, termed hus2 (hydroxyurea‐sensitive), that displays hypersensitivity to HU, aphidicolin and ionizing radiation, similar to atr mutants. In addition, cell‐cycle progression in response to replication blocks and ionizing radiation is defective in hus2 , displaying a nearly identical phenotype to atr mutants. Positional cloning of hus2 reveals a gene sequence similar to yeast Rad26/Ddc2 and ATRIP (ATR interacting protein), suggesting that hus2 encodes an Arabidopsis ATRIP ortholog.