Abstract The XPC protein, which is mutated in xeroderma pigmentosum (XP) complementation group C (XP-C), is a lesion recognition factor in NER, but it has also been shown to interact with and stimulate DNA glycosylases, to act as transcriptional co-activator and on energy metabolism adaptation. We have previously demonstrated that XP-C cells show increased mitochondrial H2O2 production with a shift between respiratory complexes I and II, leading to sensitivity to mitochondrial stress. Here we report a marked decrease in expression of the transcriptional co-activator PGC-1α, a master regulator of mitochondrial biogenesis, in XP-C cells. A transcriptional role for XPC in PGC-1α expression was discarded, as XPC knockdown did not downregulate PGC-1α expression and XPC-corrected cells still showed lower PGC-1α expression. DNA methylation alone did not explain PGC-1α silencing. In four different XP-C cell lines tested, reduction of PGC-1α expression was detected in three, all of them carrying the c.1643_1644delTG mutation (ΔTG) in XPC. Indeed, all cell lines carrying XPC ΔTG mutation, whether homozygous or heterozygous, presented decreased PGC-1α expression. However, this alteration in gene expression was not exclusive to XPC ΔTG cell lines, for other non-related cell lines also showed altered PGC-1α expression. Moreover, PGC1-α expression did not correlate with expression levels of TFAM and SDHA, known PGC-1α target-genes. In turn, PPRC1, another member of the PGC family of transcription co-activators controlling mitochondrial biogenesis, displayed a good correlation between its expression in 10 cell lines and TFAM and SDHA. Nonetheless, PGC-1α knockdown led to a slight decrease of its target-gene protein level, TFAM, and subsequently of a mtDNA-encoded gene, MT-CO2. These results indicate that PGC-1α and PPRC1 cooperate as regulators of mitochondrial biogenesis and maintenance in fibroblasts.

Carboxymethyl-glucan (CM-G) is a soluble derivative from Saccharomyces cerevisiae (1 → 3)(1 → 6)-β-D-glucan. The protective efficiency of CM-G against DNA damage in cells from patients with advanced prostate cancer (PCa), and undergoing Androgen Deprivation Therapy (ADT), was evaluated. DNA damage scores were obtained by the comet assay, both before and after treatment with CM-G. The reduction in DNA damage, ranging from 18% to 87%, with an average of 59%, was not related to the increased number of leukocytes in peripheral blood. The results demonstrate for the first time the protective effect of CM-G against DNA damage in patients with advanced PCa. Among smokers, three presented the highest reduction in DNA damage after treatment with CM-G. There was no observable relationship between DNA damage scores before and after treatment, and age, alcoholism and radiotherapy.