No abstract

In eukaryotes, DNA is compacted into a complex structure known as chromatin. The unravelling of DNA is a crucial step in DNA repair, replication, transcription and recombination as this allows access to DNA for these processes. Failure to package DNA into the nucleosome, the individual unit of chromatin, can lead to genomic instability, driving a cell into apoptosis, senescence, or cellular proliferation. Ultraviolet (UV) radiation damage causes destabilisation of chromatin integrity. UV irradiation induces DNA damage such as photolesions and subjects the chromatin to substantial rearrangements, causing the arrest of transcription forks and cell cycle arrest. Highly conserved processes known as nucleotide and base excision repair (NER and BER) then begin to repair these lesions. However, if DNA repair fails, the cell may be forced into apoptosis. The modification of various histones as well as nucleosome remodelling via ATP-dependent chromatin remodelling complexes are required not only to repair these UV-induced DNA lesions, but also for apoptosis signalling. Histone modifications and nucleosome remodelling in response to UV also lead to the recruitment of various repair and pro-apoptotic proteins. Thus, the way in which a cell responds to UV irradiation via these modifications is important in determining its fate. Failure of these DNA damage response steps can lead to cellular proliferation and oncogenic development, causing skin cancer, hence these chromatin changes are critical for a proper response to UV-induced injury.

Ultraviolet radiation (UV) from sunlight is the primary cause of skin and ocular neoplasia. Brahma (BRM) is part of the SWI/SNF chromatin remodeling complex. It provides energy for rearrangement of chromatin structure. Previously we have found that human skin tumours have a hotspot mutation in BRM and that protein levels are substantially reduced. Brm−/− mice have enhanced susceptibility to photocarcinogenesis. In these experiments, Brm−/− mice, with both or a single Trp53 allele were exposed to UV for 2 or 25 weeks. In wild type mice the central cornea and stroma became atrophic with increasing time of exposure while the peripheral regions became hyperplastic, presumably as a reparative process. Brm−/−, Trp53+/−, and particularly the Brm−/− Trp53+/− mice had an exaggerated hyperplastic regeneration response in the corneal epithelium and stroma so that the central epithelial atrophy or stromal loss was reduced. UV induced hyperplasia of the epidermis and corneal epithelium, with an increase in the number of dividing cells as determined by Ki-67 expression. This response was considerably greater in both the Brm−/− Trp53+/+ and Brm−/− Trp53+/− mice indicating that Brm protects from UV-induced enhancement of cell division, even with loss of one Trp53 allele. Cell division was disorganized in Brm−/− mice. Rather than being restricted to the basement membrane region, dividing cells were also present in the suprabasal regions of both tissues. Brm appears to be a tumour suppressor gene that protects from skin and ocular photocarcinogenesis. These studies indicate that Brm protects from UV-induced hyperplastic growth in both cutaneous and corneal keratinocytes, which may contribute to the ability of Brm to protect from photocarcinogenesis.

The phenotypic expression of quantitative characters is a function of the individual's genotype and the environment in which it is measured. In a previous reciprocal transplant study, we found that patterns of genetic differences in resistance to herbivores among adjacent subpopulations of northern red oak (Quercus rubra L.), were consistent with a local adaptation hypothesis. The goal of this study was to determine if variation in water availability may have been a mechanism responsible for these previously observed patterns. In 1989 a common garden study was initiated using acorns from maternal trees occupying either a north- or south-facing slope microhabitat in an oak-hickory forest in east central Missouri, USA. The seedlings were grown under one of two water treatments, irrigated or natural. In 1992, we utilized this experiment to examine the quantitative character of the percentage of leaf area damaged by herbivores, which is a measure of the phenotypically expressed level of resistance. Specifically, we made three predictions: (1) because northern red oak seem to grow best in mesic environments, seedlings receiving more water should show greater resistance to herbivores; (2) if the subpopulations from north- and south-facing slope microhabitats are genetically differentiated with respect to the quantitative character of resistance to herbivores, then there will be a significant effect of maternal slope microhabitat on the percentage of leaf area damaged; and (3) if the pattern of resistance to herbivores found among subpopulations reflects local adaptation to moisture levels in their own microhabitat, then we would expect to find a significant maternal slope microhabitat by water treatment interaction, with north-facing slope seedlings incurring less damage in the wetter (irrigated) treatment and south-facing slope seedlings incurring less damage in the drier (natural) treatment. Our data supported the first two predictions: seedlings in the irrigated treatment showed a significantly lower percentage of leaf area damage than those in the natural treatment, and the percentage of leaf area damaged was significantly lower on seedlings from maternal plants occupying the north-facing slope microhabitat. However, we found no significant interaction between maternal slope microhabitat and water treatment. These findings demonstrate that northern red oak supbopulations respond phenotypically to water availability, but this factor does not appear to be the underlying mechanism behind the previously observed local adaptation expressed as resistance to herbivores.