Incisions for excision

Excison implies two incisions. Plumbers and surgeons know this principle, and long ago it was put into practice by the evolutionarily ancient DNA-repair machinery. Dissection of the first incision made by the eukaryotic nucleotide-excision repair pathway has now been described by O'Donovan et al., and dissection of the second by Bardwell et al. When put together the two processes enable the replacement of a damaged piece of DNA by a new one. [...]One might predict that a category of patients will be found that are deficient in nucleotide-excision repair and also have symptoms of a recombination defect. If these striking multiple engagements reflect a general evolutionary strategy of function sharing, then intimate connections between nucleotide-excision repair and cell-cycle control or chromatin dynamics are bound to show up as well

Incisions for excision

Excison implies two incisions. Plumbers and surgeons know this principle, and long ago it was put into practice by the evolutionarily ancient DNA-repair machinery. Dissection of the first incision made by the eukaryotic nucleotide-excision repair pathway has now been described by O'Donovan et al., and dissection of the second by Bardwell et al. When put together the two processes enable the replacement of a damaged piece of DNA by a new one. [...]One might predict that a category of patients will be found that are deficient in nucleotide-excision repair and also have symptoms of a recombination defect. If these striking multiple engagements reflect a general evolutionary strategy of function sharing, then intimate connections between nucleotide-excision repair and cell-cycle control or chromatin dynamics are bound to show up as well

On General Axial Gauges for QCD

General Axial Gauges within a perturbative approach to QCD are plagued by 'spurious' propagator singularities. Their regularisation has to face major conceptual and technical problems. We show that this obstacle is naturally absent within a Wilsonian or 'Exact' Renormalisation Group approach and explain why this is so. The axial gauge turns out to be a fixed point under the flow, and the universal 1-loop running of the gauge coupling is computed.Comment: 4 pages, latex, talk presented by DFL at QCD'98, Montpellier, July 2-8, 1998; to be published in Nucl. Phys. B (Proc. Suppl.

Unscheduled DNA synthesis in xeroderma pigmentosum cells after microinjection of yeast photoreactivating enzyme.

Photoreactivating enzyme (PRE) from yeast causes a light-dependent reduction of UV-induced unscheduled DNA synthesis (UDS) when injected into the cytoplasm of repair-proficieint human fibroblasts (Zwetsloot et al., 1985). This result indicates that the exogenous PRE monomerizers UV-induced dimers in these cells competing with the endogenous excision repair. In this paper we present the results of the injection of yeast PRE on (residual) UDS in fibroblasts from different excision-deficient XP-strains representing complementation groups A, C, D, E, F, H and I (all displaying more than 10% of the UDS of wild-type

Molecular and functional analysis of the XPBC/ERCC-3 promoter: Transcription activity is dependent on the integrity of an Sp1 binding element.

The human XPBC/ERCC-3 gene, which corrects the excision-repair defect in xeroderma pigmentosum group B cells and the UV-sensitive CHO mutant 27-1 cells, appears to be expressed constitutively in various cell types and tissues. We have analysed the structure and functionality of the XPBC/ERCC-3 promoter. Transcription of the XPBC/ERCC-3 gene is initiated from heterogeneous sites, with a major startpoint mapped at position -54 (relative to the translation start codon ATG). The promoter region does not possess classical TATA and CAAT elements, but it is GC-rich and contains three putative Sp1-binding sites. In addition, there are two elements related to the cyclic AMP (cAMP)-response element (CRE) and the 12-O-tetradecanoyl phorbol-13-acetate-response element (TRE) in the 5'-flanking reg

Cloning, tissue expression, and mapping of a human photolyase homolog with similarity to plant blue-light receptors

Enzymatic photoreactivation is a DNA repair mechanism that removes UV- induced pyrimidine dimer lesions by action of a single enzyme, photolyase, and visible light. Its presence has been demonstrated in a wide variety of organisms, ranging from simple prokaryotes to higher eukaryotes. We have isolated a human gene encoding a 66-kDa protein that shows clear overall homology to known bacterial photolyase genes. The human gene product is more similar to plant blue-light receptors within class I ph

Genomic characterization of the human DNA excision repair gene ERCC-1.

In this report the genomic characterization of the human excision repair gene ERCC-1 is presented. The gene consists of 10 exons spread over approximately 15 kb. By means of a transfection assay the ERCC-1 promoter was confined to a region of + 170 bp upstream of the transcriptional start site. Classical promoter elements like CAAT, TATA and GC-boxes are absent from this region. Furthermore, ERCC-1 transcription is not UV-inducible. A possible explanation is provided for the previously reported alternative splicing of exon VIII. Analysis of ERCC-1 cDNA clones revealed the occurrence of differential polyadenylation which gives ERCC-1 transcripts of 3.4 and 3.8 kb in addition to the major 1.1 kb mRNA. Apparent evolutionary conservation of differential polyadenylation of ERCC-1 transcripts suggests a possible role for this mode of RNA processing in the ERCC-1 repair function

Evolution and mutagenesis of the mammalian excision repair gene ERCC-1

The human DNA excision repair protein ERCC-1 exhibits homology to the yeast RADIO repair protein and its longer C-terminus displays similarity to parts of the E.coli repair proteins uvrA and uvrC. To study the evolution of this 'mosaic' ERCC-1 gene we have isolated the mouse homologue. Mouse ERCC-1 harbors the same pattern of homology with RAD10 and has a comparable C-terminal extension as its human equivalent. Mutation studies show that the strongly conserved C-terminus is essential in contrast to the less conserved N-terminus which is even dispensible. The mouse ERCC-1 amino acid sequence is compatible with a previously postulated nuclear location signal and DNA-binding domain. The ERCC-1 promoter harbors a region which is highly conserved in mouse and man. Since the ERCC-1 promoter is devoid of all classical promoter elements this region may be responsible for the low constitutive level of expression in all mouse tissues and stages of embryogenesis examined