Stable and specific association between the yeast recombination and DNA repair proteins RAD1 and RAD10 in vitro.

Bardwell, Lee; Cooper, Alan; Friedberg, Errol C.

doi:10.1128/mcb.12.7.3041

Cited by 88 publications

(65 citation statements)

References 51 publications

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“…Thus these results rule out the theoretical possibility raised by these and other remarkable observations with respect to the ERCC3 gene in the yeast and Drosophila systems, namely that the ERCC3 -NER connection could be indirect, i.e. ERCC3 might control the expression of one or more (real) NER genes without being involved itself in this process (Gulyas and Donahue, 1992;Mounkes et al, 1992;Schaeffer et al, 1993 (Schiestl and Prakash, 1990;Bailly et al, 1992;Bardwell et al, 1992;Biggerstaff et al, 1993;van Vuuren et al, 1993). Using the in vitro NER assay Wood and coworkers have shown that the replication factors PCNA and HSSB (RPA) also participate in the post-incision stages of the NER reaction (Coverley et al, 1992;Shivji et al, 1992) Serizawa et al, 1993a,b) and a helicase activity (Schaeffer et al, 1993 (Gerard et al, 1991).…”

Section: Discussionmentioning

confidence: 40%

Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH).

et al. 1994

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ERCC3 was initially identified as a gene correcting the nucleotide excision repair (NER) defect of xeroderma pigmentosum complementation group B (XP‐B). The recent finding that its gene product is identical to the p89 subunit of basal transcription factor BTF2(TFIIH), opened the possibility that it is not directly involved in NER but that it regulates the transcription of one or more NER genes. Using an in vivo microinjection repair assay and an in vitro NER system based on cell‐free extracts we demonstrate that ERCC3 in BTF2 is directly implicated in excision repair. Antibody depletion experiments support the idea that the p62 BTF2 subunit and perhaps the entire transcription factor function in NER. Microinjection experiments suggest that exogenous ERCC3 can exchange with ERCC3 subunits in the complex. Expression of a dominant negative K436‐‐>R ERCC3 mutant, expected to have lost all helicase activity, completely abrogates NER and transcription and concomitantly induces a dramatic chromatin collapse. These findings establish the role of ERCC3 and probably the entire BTF2 complex in transcription in vivo which was hitherto only demonstrated in vitro. The results strongly suggest that transcription itself is a critical component for maintenance of chromatin structure. The remarkable dual role of ERCC3 in NER and transcription provides a clue in understanding the complex clinical features of some inherited repair syndromes.

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Section: Discussionmentioning

confidence: 40%

Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH).

et al. 1994

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“…[ 35 S]-labeled FLAG-DISC1 protein was synthesized using the T7 transcription/translation-coupled reticulocyte lysate system (Promega, Hampshire, UK). The translation product was partially purified by ammonium sulfate precipitation as described previously (Bardwell et al, 1992) before use in peptide array analyses.…”

Section: Methodsmentioning

confidence: 99%

Isoform-Selective Susceptibility of DISC1/Phosphodiesterase-4 Complexes to Dissociation by Elevated Intracellular cAMP Levels

Murdoch¹,

Mackie²,

Collins³

et al. 2007

J. Neurosci.

145

164

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Disrupted-in-schizophrenia 1 (DISC1) is a genetic susceptibility factor for schizophrenia and related severe psychiatric conditions. DISC1 is a multifunctional scaffold protein that is able to interact with several proteins, including the independently identified schizophrenia risk factor phosphodiesterase-4B (PDE4B). Here we report that the 100 kDa full-length DISC1 isoform (fl-DISC1) can bind members of each of the four gene, cAMP-specific PDE4 family. Elevation of intracellular cAMP levels, so as to activate protein kinase A, caused the release of PDE4D3 and PDE4C2 isoforms from fl-DISC1 while not affecting binding of PDE4B1 and PDE4A5 isoforms. Using a peptide array strategy, we show that PDE4D3 binds fl-DISC1 through two regions found in common with PDE4B isoforms, the interaction of which is supplemented because of the presence of additional PDE4B-specific binding sites. We propose that the additional binding sites found in PDE4B1 underpin its resistance to release during cAMP elevation. We identify, for the first time, a functional distinction between the 100 kDa long DISC1 isoform and the short 71 kDa isoform. Thus, changes in the expression pattern of DISC1 and PDE4 isoforms offers a means to reprogram their interaction and to determine whether the PDE4 sequestered by DISC1 is released after cAMP elevation. The PDE4B-specific binding sites encompass point mutations in mouse Disc1 that confer phenotypes related to schizophrenia and depression and that affect binding to PDE4B. Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology.

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“…Labeled proteins were partially purified by ammonium sulfate precipitation (28) and then resuspended in 50 l of Buffer A (50 mM Tris-HCl, pH 7.5, 100 mM NaCl, 10 mM MgCl 2 , 10% glycerol, 1 mM phenylmethylsulfonyl fluoride, 1 mM benzamidine HCl, 1 g/ml leupeptin, 2 g/ml aprotinin, and 1 g/ml pepstatin).…”

Section: Methodsmentioning

confidence: 99%

Processing and Joining of DNA Ends Coordinated by Interactions among Dnl4/Lif1, Pol4, and FEN-1

Tseng

Tomkinson

2004

Journal of Biological Chemistry

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The repair of DNA double-strand breaks is critical for maintaining genetic stability. In the non-homologous end-joining pathway, DNA ends are brought together by end-bridging factors. However, most in vivo DNA double-strand breaks have terminal structures that cannot be directly ligated. Thus, the DNA ends are aligned using short regions of sequence microhomology followed by processing of the aligned DNA ends by DNA polymerases and nucleases to generate ligatable termini. Genetic studies in Saccharomyces cerevisiae have implicated the DNA polymerase Pol4 and the DNA structurespecific endonuclease FEN-1(Rad27) in the processing of DNA ends to be joined by Dnl4/Lif1. In this study, we demonstrated that FEN-1(Rad27) physically and functionally interacted with both Pol4 and Dnl4/Lif1 and that together these proteins coordinately processed and joined DNA molecules with incompatible 5 ends. Because Pol4 also interacts with Dnl4/Lif1, our results have revealed a series of pair-wise interactions among the factors that complete the repair of DNA doublestrand breaks by non-homologous end-joining and provide a conceptual framework for delineating the endprocessing reactions in higher eukaryotes.The repair of DNA double-strand breaks (DSBs) 1 is critical for the maintenance of genomic integrity and stability. There are two main DSB repair pathways in eukaryotes: homologous recombination and non-homologous end joining (NHEJ) (1). In the error-free homologous recombination pathway, an intact homologous DNA duplex acts as a template for repair, resulting in the accurate restoration of the broken DNA molecule. By contrast, in NHEJ, the two broken ends are simply rejoined to one another in a process that frequently causes loss and/or gain of nucleotides at the break site and occasionally results in the joining of previously unlinked DNA molecules. Notably, defects in the repair of DSBs by either homologous recombination or NHEJ have been linked with cancer predisposition (2, 3).Studies with mammalian cells identified the DNA-dependent protein kinase (DNA-PK), which is composed of the DNA end binding Ku70/Ku80 heterodimer and the DNA-PK catalytic subunit, and the DNA ligase IV/XRCC4 complex as key NHEJ factors (4). In Saccharomyces cerevisiae, Hdf1/Hdf2 and Dnl4/Lif1 are the functional homologs of Ku70/Ku80 and DNA ligase IV/XRCC4, respectively (4). Although yeast lacks a DNA-PK catalytic subunit homolog, genetic studies have revealed that the Rad50/Mre11/Xrs2 complex is a key player in NHEJ (4 -7). Using purified protein complexes, it has been shown that the Rad50/Mre11/Xrs2 complex has robust endbridging activity and specifically stimulates intermolecular DNA joining by Dnl4/Lif1 (8). Furthermore, efficient intermolecular DNA joining mediated by the Rad50/Mre11/Xrs2 and Dnl4/Lif1 complexes was dependent upon Hdf1/Hdf2 at physiological salt concentrations (8). Based on these results, it seems likely that Hdf1/Hdf2 enhances the recruitment of the Rad50/ Mre11/Xrs2 end-bridging complex to DNA ends and that Dnl4/ Lif1 joins the res...

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Stable and specific association between the yeast recombination and DNA repair proteins RAD1 and RAD10 in vitro.

Cited by 88 publications

References 51 publications

Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH).

Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH).

Isoform-Selective Susceptibility of DISC1/Phosphodiesterase-4 Complexes to Dissociation by Elevated Intracellular cAMP Levels

Processing and Joining of DNA Ends Coordinated by Interactions among Dnl4/Lif1, Pol4, and FEN-1

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