Differential roles for Chk1 and FANCD2 in ATR-mediated signalling for psoralen photoactivation-induced senescence.

Cellular senescence is a stress-inducible, naturally irreversible cell cycle arrest, which is likely linked with ageing. Premature ageing of the skin is a prominent side effect of psoralen photoactivation, which is used for the treatment of various skin disorders. Previously, we have shown that DNA interstrand crosslink formation by photoactivated psoralens induces a senescent phenotype in primary fibroblasts that is mediated by Ataxia telangiectasia-mutated and Rad3-related (ATR) kinase.

Pyoderma gangrenosum following cardiac surgery.

Pyoderma gangrenosum appeared in multiple incision sites after coronary bypass surgery.

Conserved interactions of the splicing factor Ntr1/Spp382 with proteins involved in DNA double-strand break repair and telomere metabolism.

The ligation of DNA double-strand breaks in the process of non-homologous end-joining (NHEJ) is accomplished by a heterodimeric enzyme complex consisting of DNA ligase IV and an associated non-catalytic factor. This DNA ligase also accounts for the fatal joining of unprotected telomere ends. Hence, its activity must be tightly controlled.

Mitochondrial electron transport chain activity is not involved in ultraviolet A (UVA)-induced cell death.

Ultraviolet A (UVA), the long wavelength part of the sun's ultraviolet radiation, elicits its harmful effects through production of reactive oxygen species. In this study, we have tested the hypothesis that the mitochondrial electron transport chain, the main source of reactive oxygen species in cells, importantly contributes to UVA-induced cell damage. Model cell lines completely lacking a mitochondrial electron transport chain (rho(0)-cells) were not protected against UVA-induced cell death.

Senescence of human fibroblasts after psoralen photoactivation is mediated by ATR kinase and persistent DNA damage foci at telomeres.

Cellular senescence is a phenotype that is likely linked with aging. Recent concepts view different forms of senescence as permanently maintained DNA damage responses partially characterized by the presence of senescence-associated DNA damage foci at dysfunctional telomeres. Irradiation of primary human dermal fibroblasts with the photosensitizer 8-methoxypsoralen and ultraviolet A radiation (PUVA) induces senescence.

Complete remission of Merkel cell carcinoma of the scalp with local and regional metastases after topical treatment with dinitrochlorbenzol.

Merkel cell carcinoma (MCC) is a highly aggressive tumor with a high percentage of recurrence, metastatic spread, and mortality. Treatment of metastasized MCC is not standardized and prognosis of metastasized MCC is often poor. Current protocols recommend surgery, adjuvant radiation therapy, and often lymph node dissection to prevent recurrences.

Human dermal fibroblasts escape from the long-term phenocopy of senescence induced by psoralen photoactivation.

We have previously shown that following psoralen photoactivation (PUVA treatment) human dermal fibroblasts undergo long-term growth arrest as well as morphological and functional changes reminiscent of cellular senescence [ 1 ]. In the absence of molecular data on what constitutes normal senescence, it has been difficult to decide whether these PUVA-induced changes reflect cellular senescence or rather a mimic thereof. We herein report that PUVA-induced growth arrest, the senescent phenotype with long-term induction of senescence-associated beta-galactosidase, as well as increased expression of matrix metalloprotease-1 are fully reversible at days 100 to 130 post PUVA treatment in four independently tested fibroblast strains.