[Low efficiency of DNA repair system in mitochondria].
Under the action of endogenous reactive oxygen species and exogenous chemical and physical agents, significantly more lesions occur in mitochondrial DNA (mtDNA) than in nuclear DNA (nDNA). However, the mechanisms of DNA repair in mitochondria are less efficient that in the nuclei. The mechanisms of nucleotide excision repair capable of removing UV-induced lesions or other complex adducts induced by chemical compounds are not operative in mitochondria at all. At the same time, mitochondria of some kinds contain a photoreactivation enzyme providing monomerization of cyclobutane pyrimidine dimers. Also, the enzyme system for DNA base excision repair (BER) and O6-alkylguanine-DNA alkyl transferase are functional in mitochondria. However, the rate of BER-controlled repair of lesions in mtDNA is lower than that in nDNA. The literature data suggest that the controlling system for the delay of DNA replication till the repair complexion (cell cycle checkpoint) cannot be provided in mitochontria. Besides, it remains unclear whether the mismatch repair mechanisms are operable in mammalian mitochondria. On the other hand, double-strand breaks in mammalian mtDNA are possibly repaired by involving the DNA-dependent protein kinase complex, and the process of BER is affected by poly(ADP-ribosyl)ation of proteins. Possible consequences of induction of the increased level of damage in mtDNA and the low efficiency of repair systems in mitochondria are discussed in this review.
Gaziev
A I
AI
Institute of Theoretical and Experimental Biophysics RAS, Pushchino. gaziev@venus.iteb.serpukhov.su
Podlutskiĭ
A Ia
AIa
D000818:Animals; D016922:Cellular Senescence; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000528:radiation effects; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D014466:Ultraviolet Rays
D004272:DNA, Mitochondrial; D019853:O(6)-Methylguanine-DNA Methyltransferase; D045647:DNA Glycosylases; C036401:deoxyribopyrimidine endonucleosidase