Adaptive Melanin Response of the Soil Fungus Aspergillus niger to UV Radiation Stress at “Evolution Canyon”, Mount Carmel, Israel

BACKGROUND:Adaptation is an evolutionary process in which traits in a population are tailored by natural selection to better meet the challenges presented by the local environment. The major discussion relating to natural selection concerns the portraying of the cause and effect relationship between a presumably adaptive trait and selection agents generating it. Therefore, it is necessary to identify trait(s) that evolve in direct response to selection, enhancing the organism's fitness. "Evolution Canyon" (EC) in Israel mirrors a microcosmic evolutionary system across life and is ideal to study natural selection and local adaptation under sharply, microclimatically divergent environments. The south-facing, tropical, sunny and xeric "African" slope (AS) receives 200%-800% higher solar radiation than the north-facing, temperate, shady and mesic "European" slope (ES), 200 meters apart. Thus, solar ultraviolet radiation (UVR) is a major selection agent in EC influencing the organism-environment interaction. Melanin is a trait postulated to have evolved for UV-screening in microorganisms. Here we investigate the cause and effect relationship between differential UVR on the opposing slopes of EC and the conidial melanin concentration of the filamentous soil fungus Aspergillus niger. We test the working hypothesis that the AS strains exhibit higher melanin content than strains from the ES resulting in higher UV resistance. METHODOLOGY/PRINCIPAL FINDINGS:We measured conidial melanin concentration of 80 strains from the EC using a spectrophotometer. The results indicated that mean conidial melanin concentration of AS strains were threefold higher than ES strains and the former resisted UVA irradiation better than the latter. Comparisons of melanin in the conidia of A. niger strains from sunny and shady microniches on the predominantly sunny AS and predominantly shady ES indicated that shady conditions on the AS have no influence on the selection on melanin; in contrast, the sunny strains from the ES displayed higher melanin concentrations. CONCLUSIONS/SIGNIFICANCE:We conclude that melanin in A. niger is an adaptive trait against UVR generated by natural selection

PI 3 Kinase Related Kinases-Independent Proteolysis of BRCA1 Regulates Rad51 Recruitment during Genotoxic Stress in Human Cells

The function of BRCA1 in response to ionizing radiation, which directly generates DNA double strand breaks, has been extensively characterized. However previous investigations have produced conflicting data on mutagens that initially induce other classes of DNA adducts. Because of the fundamental and clinical importance of understanding BRCA1 function, we sought to rigorously evaluate the role of this tumor suppressor in response to diverse forms of genotoxic stress.We investigated BRCA1 stability and localization in various human cells treated with model mutagens that trigger different DNA damage signaling pathways. We established that, unlike ionizing radiation, either UVC or methylmethanesulfonate (MMS) (generating bulky DNA adducts or alkylated bases respectively) induces a transient downregulation of BRCA1 protein which is neither prevented nor enhanced by inhibition of PIKKs. Moreover, we found that the proteasome mediates early degradation of BRCA1, BARD1, BACH1, and Rad52 implying that critical components of the homologous recombination machinery need to be functionally abrogated as part of the early response to UV or MMS. Significantly, we found that inhibition of BRCA1/BARD1 downregulation is accompanied by the unscheduled recruitment of both proteins to chromatin along with Rad51. Consistently, treatment of cells with MMS engendered complete disassembly of Rad51 from pre-formed ionizing radiation-induced foci. Following the initial phase of BRCA1/BARD1 downregulation, we found that the recovery of these proteins in foci coincides with the formation of RPA and Rad51 foci. This indicates that homologous recombination is reactivated at later stage of the cellular response to MMS, most likely to repair DSBs generated by replication blocks.Taken together our results demonstrate that (i) the stabilities of BRCA1/BARD1 complexes are regulated in a mutagen-specific manner, and (ii) indicate the existence of mechanisms that may be required to prevent the simultaneous recruitment of conflicting signaling pathways to sites of DNA damage

Endogenous phospholipid metabolite containing topical product inhibits ultraviolet light-induced inflammation and DNA damage in human skin.

Background: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous components of the human epidermis and are generated from phospholipids in the stratum granulosum. PEA has been shown to exert potent antioxidant and anti-inflammatory activities. The endogenous organic osmolytes such as betaine and sarcosine control skin humidity, but have also been shown to inhibit ultraviolet (UV) light-induced oxidative stress in keratinocytes. Objectives: To investigate the effect of a PEA-and organic osmolyte-containing topical product (Physiogel AI (R)) on the development of UV light-induced erythema, thymine dimer formation and p53 tumor suppressor gene activation, as well as intercellular adhesion molecule 1 (ICAM-1) and Ki67 expression in normal human skin. Methods: The UV-induced erythema was measured by a spectrofluorometric method. Thymine dimers, p53, ICAM-1 and Ki67 were detected in skin biopsies using immunohistochemistry. Results: Physiogel AI cream significantly inhibited the development of UV light-induced erythema and thymine dimer formation in normal human skin, but did not alter the number of Ki67+ proliferating keratinocytes and the expression of p53 and ICAM-1. Conclusions: Our results suggest that PEA and organic osmolytes might represent a new generation of compounds which suppress UV-induced photodamage. Copyright (c) 2007 S. Karger AG, Base