title: Phosphorylation-regulated binding of Ctp1 to Nbs1 is critical for repair of DNA double-strand breaks.
abstract: Repair of DNA double-strand breaks (DSBs) is critical for cell survival and for maintaining genome stability in eukaryotes. In Schizosaccharomyces pombe, the Mre11-Rad50-Nbs1 (MRN) complex and Ctp1 cooperate to perform the initial steps that process and repair these DNA lesions via homologous recombination (HR). While Ctp1 is recruited to DSBs in an MRN-dependent manner, the specific mechanism of this process remained unclear. We recently found that Ctp1 is phosphorylated on a domain rich in putative Casein kinase 2 (CK2) phosphoacceptor sites that resembles the SDTD repeats of Mdc1. Furthermore, phosphorylation of this motif is required for interaction with the FHA domain of Nbs1 that localizes Ctp1 to DSB sites. Here, we review and discuss these findings, and we present new data that further characterize the cellular consequences of mutating CK2 phosphorylation motifs of Ctp1, including data showing that these sites are critical for meiosis.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Dodson
authors.forename: Oliver
authors.initials: O
authors.lastname: Limbo
authors.forename: Devon
authors.initials: D
authors.lastname: Nieto
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
mesh_terms: D047390:Casein Kinase II / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D010766:Phosphorylation; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C525888:Ctp1 protein, S pombe; D004268:DNA-Binding Proteins; C478035:Nbs1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D047390:Casein Kinase II