Victor A. Tron

Mammalian DNA mismatch repair protects cells from UVB-induced DNA damage by facilitating apoptosis and p53 activation.

DNA mismatch repair (MMR) is integral to the maintenance of genomic stability and more recently has been demonstrated to affect apoptosis and cell cycle arrest in response to a variety of adducts induced by exogenous agents. Comparing Msh2-null and wildtype mouse embryonic fibroblasts (MEFs), both primary and transformed, we show that Msh2 deficiency results in increased survival post-UVB, and that UVB-induced apoptosis is significantly reduced in Msh2-deficient cells. Furthermore, p53 phosphorylation at serine 15 is delayed or diminished in Msh2-deficient cells, suggesting that Msh2 may act upstream of p53 in a post-UVB apoptosis or growth arrest response pathway. Taken together, these data suggest that MMR heterodimers containing Msh2 may function as a sensor of UVB-induced DNA damage and influence the initiation of UVB-induced apoptosis, thus implicating MMR in protecting against UV-induced tumorigenesis.

p53-dependent regulation of heat shock protein 72

Summary Backgroundu2003p53 is a key regulator of the cellular stress response. p53 modulates the transcription of several genes.

Immunological diagnosis of cutaneous-pulmonary hypersensitivity vasculitis.

A 47-year-old woman had episodic dyspnoea, fatigue, chest radiograph opacifications, and palpable purpura whose biopsy showed leucocytoclastic vasculitis. Negative immunoglobulin A immunofluorescence staining and clinical exclusion of other disorders narrowed her diagnosis to cutaneous pulmonary hypersensitivity vasculitis.