Aberrant base excision repair pathway of oxidatively damaged DNA: Implications for degenerative diseases
FREE RADICAL BIOLOGY AND MEDICINE
Authors: Talhaoui, Ibtissam; Matkarimov, Bakhyt T.; Tchenio, Thierry; Zharkov, Dmitry O.; Saparbaev, Murat K.
Abstract
In cellular organisms composition of DNA is constrained to only four nucleobases A, G, T and C, except for minor DNA base modifications such as methylation which serves for defence against foreign DNA or gene expression regulation. Interestingly, this severe evolutionary constraint among other things demands DNA repair systems to discriminate between regular and modified bases. DNA glycosylases specifically recognize and excise damaged bases among vast majority of regular bases in the base excision repair (BER) pathway. However, the mismatched base pairs in DNA can occur from a spontaneous conversion of 5-methylcytosine to thymine and DNA polymerase errors during replication. To counteract these mutagenic threats to genome stability, cells evolved special DNA repair systems that target the non-damaged DNA strand in a duplex to remove mismatched regular DNA bases. Mismatch-specific adenine-and thymine-DNA glycosylases (MutY/MUTYH and TDG/MBD4, respectively) initiated BER and mismatch repair (MMR) pathways can recognize and remove normal DNA bases in mismatched DNA duplexes. Importantly, in DNA repair deficient cells bacterial MutY, human TDG and mammalian MMR can act in the aberrant manner: MutY and TDG removes adenine and thymine opposite misincorporated 8-oxoguanine and damaged adenine, respectively, whereas MMR removes thymine opposite to O-6-methylguanine. These unusual activities lead either to mutations or futile DNA repair, thus indicating that the DNA repair pathways which target non-damaged DNA strand can act in aberrant manner and introduce genome instability in the presence of unrepaired DNA lesions. Evidences accumulated showing that in addition to the accumulation of oxidatively damaged DNA in cells, the aberrant DNA repair can also contribute to cancer, brain disorders and premature senescence. For example, the aberrant BER and MMR pathways for oxidized guanine residues can lead to trinucleotide expansion that underlies Huntington's disease, a severe hereditary neurodegenerative syndrome. This review summarises the present knowledge about the aberrant DNA repair pathways for oxidized base modifications and their possible role in age-related diseases.
Genetic variability of phytic acid phosphorus and inorganic phosphorus in cultivated groundnut (Arachis hypogaea L.)
PLANT GENETIC RESOURCES-CHARACTERIZATION AND UTILIZATION
Authors: Hande, Poonam A.; Mondal, Suvendu; Badigannavar, A. M.; D'Souza, S. F.
Abstract
The presence of excessive phytic acids in foods exerts undesirable antinutritional effects while their agricultural product is utilized as food for humans and as fodder for animals. In this study, 40 cultivated groundnut genotypes were grown in two years and used to estimate the phytic acid phosphorus (PAP) and inorganic phosphorus (InP) contents. The PAP content differed significantly (P = 0.01) among the genotypes and ranged from 149.3 to 315.0mg PAP/100 g seed with an average of 227.6mg PAP/100 g seed. The genotypes TG 17 and TG 67 had the highest (315 mg) and the lowest (149.3 mg) PAP content, respectively. The InP content ranged from 58.7 mg/100 g seed in the SG 99 genotype to 102.6 mg/100 g seed in the TG 40 genotype, with a mean of 82.6 mg/100 g seed. The ratio of InP to PAP varied from 0.24 to 0.56. A significantly higher InP: PAP ratio was found in the genotypes TKG 19A, TAG 24, TG 37A, TBG 39 (TDG 39), TG 51, TG 67 and GG 7, which was due to either an increase in InP content or a decrease in PAP content.
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