The UVSSA protein is part of a genome integrity homeostasis network with links to transcription-coupled DNA repair and ATM signaling.

SignificanceTranscription-coupled repair (TCR) involves four core proteins: CSA, CSB, USP7, and UVSSA. CSA and CSB are mutated in the severe human neurocutaneous disease Cockayne syndrome. In contrast UVSSA is a mild photosensitive disease in which a mutated protein sequence prevents recruitment of USP7 protease to deubiquitinate and stabilize CSB.

Beyond xeroderma pigmentosum: DNA damage and repair in an ecological context. A tribute to James E. Cleaver.

The ability to repair DNA is a ubiquitous characteristic of life on Earth and all organisms possess similar mechanisms for dealing with DNA damage, an indication of a very early evolutionary origin for repair processes. James E. Cleaver's career (initiated in the early 1960s) has been devoted to the study of mammalian ultraviolet radiation (UVR) photobiology, specifically the molecular genetics of xeroderma pigmentosum and other human diseases caused by defects in DNA damage recognition and repair.

Effects of UVB on interactions between Schistosoma mansoni and Biomphalaria glabrata.

Ultraviolet B (UVB, 280-315nm) radiation is detrimental to both of larvae of the digenetic trematode Schistosoma mansoni and its snail intermediate host, Biomphalaria glabrata. We explored effects of UVB on three aspects of the interaction between host and parasite: survival of infected snails, innate susceptibility and resistance of snails to infection, and acquired resistance induced by irradiated miracidia. Snails infected for 1 week showed significantly lower survival than uninfected snails following irradiation with a range of UVB intensities.

Sublethal effects of ultraviolet b radiation on miracidia and sporocysts of Schistosoma mansoni: intramolluscan development, infectivity, and photoreactivation.

Schistosoma mansoni occurs in tropical regions where levels of ultraviolet B (UVB; 290-320 nm) light are elevated. However, the effects of UVB on parasite transmission are unknown. This study examines effects of UVB on the miracidia and sporocysts of S.

Pol eta is required for DNA replication during nucleotide deprivation by hydroxyurea.

Hydroxyurea reduces DNA replication by nucleotide deprivation, whereas UV damage generates DNA photoproducts that directly block replication fork progression. We show that the low fidelity class Y polymerase Pol eta is recruited to proliferating cell nuclear antigen at replication forks both by hydroxyurea and UV light. Under nucleotide deprivation, Pol eta allows cells to accumulate at the G1/S boundary by facilitating slow S-phase progression and promotes apoptosis.

Cockayne syndrome exhibits dysregulation of p21 and other gene products that may be independent of transcription-coupled repair.

Cockayne syndrome (CS) is a progressive childhood neurodegenerative disorder associated with a DNA repair defect caused by mutations in either of two genes, CSA and CSB. These genes are involved in nucleotide excision repair (NER) of DNA damage from ultraviolet (UV) light, other bulky chemical adducts and reactive oxygen in transcriptionally active genes (transcription-coupled repair, TCR). For a long period it has been assumed that the symptoms of CS patients are all due to reduced TCR of endogenous DNA damage in the brain, together with unexplained unique sensitivity of specific neural cells in the cerebellum.

Lethal and sub-lethal effects of UVB on juvenile Biomphalaria glabrata (Mollusca: Pulmonata).

Although Schistosoma mansoni occurs mainly in the tropics, where intense levels of solar radiation are present, the impact of ultraviolet (UV) light on schistosome transmission is not known. The purpose of this study was to investigate potential effects of UVB (290-320nm) on juvenile Biomphalaria glabrata, the snail intermediate host of S. mansoni.

Distribution of mycosporine-like amino acids in the sea hare Aplysia dactylomela: effect of diet on amounts and types sequestered over time in tissues and spawn.

We investigated the interaction of diet and accumulation of UV-absorbing mycosporine-like amino acids (MAAs) in body tissues and spawn of the sea hare Aplysia dactylomela to determine if MAA accumulation reflects type and level of dietary intake. Food sources were the red algae Acanthophora spicifera, Centroceras clavulatum, and Laurencia sp., and the green alga, Ulva lactuca.

Considerations for evaluating ultraviolet radiation-induced genetic damage relative to Antarctic ozone depletion.

Springtime ozone depletion over the Antarctic results in increased UVB in local marine environments. It has been established that decreases in primary productivity occur with decreases in ozone concentrations, but the impact of increased UVB on the functioning and stability of the ecosystem has not yet been determined. Very little has been done to evaluate the potential for genetic damage caused by the increase in UVB, and this type of damage is most significant relative to the fitness and maintenance of populations.

Mutation and expression of the XPA gene in revertants and hybrids of a xeroderma pigmentosum cell line.

A series of ultraviolet (UV)-resistant cell lines have been generated from a UV-sensitive XP group A cell line homozygous for a stop codon (TGA) in the chromosome 9 XPA gene. Three lines generated by chemical mutagenesis acquired the ability to excise (6-4) photoproducts but not cyclobutane dimers from the whole genome; two lines generated by a fusion procedure with hamster cells acquired the ability to excise both (6-4) photoproducts and cyclobutane dimers from the whole genome. A central region of the hamster XPA gene was cloned and sequenced.

Ozone depletion: ultraviolet radiation and phytoplankton biology in antarctic waters.

The springtime stratospheric ozone (O3) layer over the Antarctic is thinning by as much as 50 percent, resulting in increased midultraviolet (UVB) radiation reaching the surface of the Southern Ocean. There is concern that phytoplankton communities confined to near-surface waters of the marginal ice zone will be harmed by increased UVB irradiance penetrating the ocean surface, thereby altering the dynamics of Antarctic marine ecosystems. Results from a 6-week cruise (Icecolors) in the marginal ice zone of the Bellingshausen Sea in austral spring of 1990 indicated that as the O3 layer thinned: (i) sea surface- and depth-dependent ratios of UVB irradiance (280 to 320 nanometers) to total irradiance (280 to 700 nanometers) increased and (ii) UVB inhibition of photosynthesis increased.

Correction of excision repair in xeroderma pigmentosum by hamster chromosome fragments involves both classes of pyrimidine dimers.

The ultraviolet light-sensitive phenotype of xeroderma pigmentosum (XP) has been corrected by the incorporation into XP cells of small chromosome fragments from Chinese hamster ovary cells. Like normal human and hamster cells, these XP-hamster hybrids are able to excise both of the photoproducts produced by ultraviolet light: cyclobutane pyrimidine dimers and the minor photoproduct, (6-4) pyrimidine-pyrimidone dimers. This excision capacity contrasts with that of an XP revertant, of the same cell line used in this study, which is able to excise only the (6-4) photoproducts.

Repair-deficient xeroderma pigmentosum cells made UV light resistant by fusion with X-ray-inactivated Chinese hamster cells.

Xeroderma pigmentosum (XP) is an autosomal recessive human disease, characterized by an extreme sensitivity to sunlight, caused by the inability of cells to repair UV light-induced damage to DNA. Cell fusion was used to transfer fragments of Chinese hamster ovary (CHO) chromosomes into XP cells. The hybrid cells exhibited UV resistance and DNA repair characteristics comparable to those expressed by CHO cells, and their DNA had greater homology with CHO DNA than did the DNA from XP cells.

Excision repair in xeroderma pigmentosum group C but not group D is clustered in a small fraction of the total genome.

DNA repair in xeroderma pigmentosum complementation groups C and D occurs at a low level. Measurements of pyrimidine dimers remaining in bulk DNA from the whole genome indicated very little excision in either complementation group. The repair sites in group C cells were, however, clustered together in small regions of the genome which appeared to be mended nearly as efficiently as the whole genome is mended in normal cells, while repair in group D cells was randomly distributed.