Twelve aldehyde dehydrogenase (ALDH) genes have been identified in humans. These genes, located on different chromosomes, encode a group of enzymes which oxidizes varieties of aliphatic and aromatic aldehydes. Metabolic disorders and clinical problems associated with mutations of ALDH1, ALDH2, ALDH4, ALDH10 and succinic semialdehyde (SSDH) genes have been emerged. Comparison of the human ALDHs indicates a wide range of divergency (Ͼ 80ϪϽ 15% identity at the protein sequence level) among them. However, several protein regions, some of which are implicated in functional activities, are conserved in the family members.The phylogenic tree constructed of 56 ALDH sequences of humans, animals, fungi, protozoa and eubacteria, suggests that the present-day human ALDH genes were derived from four ancestral genes that existed prior to the divergence of Eubacteria and Eukaryotes. The neighbor-joining tree derived from 12 human ALDHs and antiquitin indicates that diversification within the ALDH1/2/5/6 gene cluster occurred during the Neoproterozoic period (about 800 million years ago). Duplication in the ALDH 3/10/7/8 gene cluster occurred in Phanerozoic period (about 300 million years ago). Separations of ALDH3/ALDH10 and that of ALDH7/ALDH8 had occurred during the period of appearance and radiation of mammalian species.Keywords : gene family ; genomic organization; genetic disease; genetic variant; detoxification; evolution ; phylogenetic tree. This paper reviews the functional and structural diversity and Aldehyde dehydrogenases [aldehyde: NAD(P) ϩ oxidoreductase] are a group of enzymes catalyzing the conversion of alde-evolution of the human ALDH gene family.There is no uniform nomenclature system for human and hydes to the corresponding acids by means of an NAD(P) ϩ -dependent virtually irreversible reaction. ALDHs are widely dis-animal ALDH genes and enzymes. Therefore, commonly used abbreviated human gene symbols (GBD symbols) are used for tributed from bacteria to humans.Mammalian ALDH activity was first observed in ox liver genes (in italic) and enzymes (in non-italic) in the present review. GenBank identification numbers are also given. nearly 50 years ago [1] and thereafter several types of ALDH were distinguished based on their physico-chemical characteristics, enzymological properties, subcellular localization, and tissue distribution [2Ϫ4]. Two ALDH genes were cloned and char-Members of ALDH families acterized in 1985 [5]. At the present time, ten non-allelic genes Twelve known human ALDH genes and corresponding enhave been identified in the human ALDH family. In addition, zymes are listed in Proteins (enzyme subunits) encoded by these genes consist probably exist in other mammals. Protein sequences, genes and/ of about 500 amino acid residues. Catalytically active forms of or cDNAs for more than 50 animals, fungi, and bacterial ALDHs the enzymes are homodimers (ALDH3, ALDH4), homotetrahave been reported. mers (ALDH1, ALDH2, ALDH9, MMSDD) or unknown.

The UV components of sunlight (UVA and UVB) are implicated in the etiology of human skin cancer. The underlying mechanism of action for UVB carcinogenicity is well defined; however, the mechanistic involvement of UVA in carcinogenesis is not fully delineated. We investigated the genotoxicity of UVA1 versus UVB in the overall genome and in the p53 tumor suppressor gene in normal human skin fibroblasts. Immuno-dot blot analysis identified the cis-syn cyclobutane pyrimidine-dimer (CPD) as a distinctive UVBinduced lesion and confirmed its formation in the genomic DNA of UVA1-irradiated cells dependent on radiation dose. HPLC͞tandem MS analysis showed an induction of 8-oxo-7,8-dihydro-2-deoxyguanosine in the genomic DNA of UVA1-irradiated cells only. Mapping of DNA damages by terminal transferase-dependent PCR revealed preferential, but not identical, formation of polymeraseblocking lesions and͞or strand breaks along exons 5-8 of the p53 gene in UVB-and UVA1-irradiated cells. The UVB-induced lesions detected by terminal transferase-PCR were almost exclusively mapped to pyrimidine-rich sequences; however, the UVA1-induced lesions were mapped to purine-and pyrimidine-containing sequences along the p53 gene. Cleavage assays with lesion-specific DNA repair enzymes coupled to ligation-mediated PCR showed preferential, but not identical, formation of CPDs along the p53 gene in UVB-and UVA1-irradiated cells. Additionally, dosedependent formation of oxidized and ring-opened purines and abasic sites was established in the p53 gene in only UVA1-irradiated cells. We conclude that UVA1 induces promutagenic CPDs and oxidative DNA damage at both the genomic and nucleotide resolution level in normal human skin fibroblasts. U ltraviolet (UV) irradiation from the sun is linked to basal and squamous cell carcinomas of the skin and cutaneous malignant melanoma in humans (1-3). The etiologically relevant UV wavelengths for development of these diseases are UVA (320-400 nm) and UVB (280-320 nm) (4, 5). UVA constitutes the major proportion of the solar UV reaching the surface of the Earth (Ϸ95%). The remaining fraction is the residual UVB, which is not absorbed by passage through the stratospheric ozone layer (6, 7). Biologically, however, UVB is a few orders of magnitude more potent than UVA in inducing photocarcinogenesis (8).The carcinogenic effect of UVB is irrefutably ascribed to its ability to produce promutagenic DNA lesions including cis-syn cyclobutane pyrimidine-dimers (CPDs) and to a lesser extent pyrimidine (6-4) pyrimidone photoproducts [(6-4)PPs]. The carcinogenicity of UVA is partly attributed to its mutagenicity; however, the mechanistic involvement of UVA in mutagenesis remains controversial. The latter is caused by the ambiguous DNA damaging effects of this wavelength (4, 5).Generally, the poor absorption of UVA by DNA supports the notion that UVA indirectly triggers mutagenesis via photosensitization reactions. Presumably, UVA sensitizes intracellular chromophores, thereby generating reactive oxygen species, which in tu...

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Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output.DOI: http://dx.doi.org/10.7554/eLife.03781.001