Widespread alteration of the genomic DNA is a hallmark of tumors, and alteration of genes involved in DNA maintenance have been shown to contribute to the tumorigenic process. The DNA polymerase of Saccharomyces cerevisiae is required for error-prone repair following DNA damage and consists of a complex between three proteins, scRev1, scRev3, and scRev7. Here we describe a candidate human homolog of S. cerevisiae Rev7 (hREV7), which was identified in a yeast two-hybrid screen using the human homolog of S. cerevisiae Rev3 (hREV3). The hREV7 gene product displays 23% identity and 53% similarity with scREV7, as well as 23% identity and 54% similarity with the human mitotic checkpoint protein hMAD2. hREV7 is located on human chromosome 1p36 in a region of high loss of heterozygosity in human tumors, although no alterations of hREV3 or hREV7 were found in primary human tumors or human tumor cell lines. The interaction domain between hREV3 and hREV7 was determined and suggests that hREV7 probably functions with hREV3 in the human DNA polymerase complex. In addition, we have identified an interaction between hREV7 and hMAD2 but not hMAD1. While overexpression of hREV7 does not lead to cell cycle arrest, we entertain the possibility that it may act as an adapter between DNA repair and the spindle assembly checkpoint. DNA damage is induced by a variety of endogenous and exogenous factors (1). Such DNA alterations include reactive oxygen damage, deamination, loss of nucleotides, nucleotide modifications, and DNA strand breaks. DNA damage repair has evolved to cope with these environmental and mutageninduced DNA alteration and plays a central role in maintaining the genetic stability of the organism (2, 3).Extensive studies of bacterial and yeast systems have identified components of the DNA repair machinery. In the yeast Saccharomyces cerevisiae, pyrimidine dimers induced by UV radiation damage are corrected by the RAD3 excision repair, the RAD6 postreplication repair, and the RAD52 recombinational repair pathways (for a review see Ref. 4). Interestingly, the removal of UV damage by the RAD6 pathway occurs by both error-free and error-prone (mutagenic) mechanisms (5, 6). The mutagenic repair of UV damage has been shown to require the UV revertible genes, REV1, REV3, and REV7, a lesion bypass polymerase complex consisting of a deoxycytidyl-transferase (Rev1), a polymerase catalytic subunit (Rev3), and a polymerase accessory protein (Rev7) (for review see Refs. 7 and 8). This polymerase complex has been termed polymerase .

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Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.

Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC.

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