title: Conserved interactions of the splicing factor Ntr1/Spp382 with proteins involved in DNA double-strand break repair and telomere metabolism.
abstract: The ligation of DNA double-strand breaks in the process of non-homologous end-joining (NHEJ) is accomplished by a heterodimeric enzyme complex consisting of DNA ligase IV and an associated non-catalytic factor. This DNA ligase also accounts for the fatal joining of unprotected telomere ends. Hence, its activity must be tightly controlled. Here, we describe interactions of the DNA ligase IV-associated proteins Lif1p and XRCC4 of yeast and human with the putatively orthologous G-patch proteins Ntr1p/Spp382p and NTR1/TFIP11 that have recently been implicated in mRNA splicing. These conserved interactions occupy the DNA ligase IV-binding sites of Lif1p and XRCC4, thus preventing the formation of an active enzyme complex. Consistently, an excess of Ntr1p in yeast reduces NHEJ efficiency in a plasmid ligation assay as well as in a chromosomal double-strand break repair (DSBR) assay. Both yeast and human NTR1 also interact with PinX1, another G-patch protein that has dual functions in the regulation of telomerase activity and telomere stability, and in RNA processing. Like PinX1, NTR1 localizes to telomeres and associates with nucleoli in yeast and human cells, suggesting a function in localized control of DSBR.
authors: Department of Dermatology, University of Cologne, Cologne, Germany. gernot.herrmann@uni-koeln.de
authors: Gernot
authors: G
authors: Herrmann
authors: Sanja
authors: S
authors: Kais
authors: Jan
authors: J
authors: Hoffbauer
authors: Kijwasch
authors: K
authors: Shah-Hosseini
authors: Nicole
authors: N
authors: Brüggenolte
authors: Heiko
authors: H
authors: Schober
authors: Margaret
authors: M
authors: Fäsi
authors: Primo
authors: P
authors: Schär
mesh_terms: D018797:Cell Cycle Proteins; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D000072260:RNA Splicing Factors; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C114091:LIF1 protein, S cerevisiae; C441270:NEJ1 protein, S cerevisiae; D009687:Nuclear Proteins; C440808:PINX1 protein, human; D000072260:RNA Splicing Factors; D029701:Saccharomyces cerevisiae Proteins; C507652:Spp382 protein, S cerevisiae; C485860:TFIP11 protein, human; D034501:Telomere-Binding Proteins; D025521:Tumor Suppressor Proteins