OBJECTIVE To investigate the molecular etiology of 2 unrelated patients with a multisystem mitochondrial disorder accompanied by optic atrophy in one of them. DESIGN Clinical examination and neurophysiological, radiological, morphological, and molecular analyses. SETTING Tertiary care neuromuscular clinic and molecular genetics laboratory. PATIENTS A 65-year-old man (patient 1) with dysch...

Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase g, which is mutated in the variant form of the cancer predisposition di...

Oxidative phosphorylation (OXPHOS), the intracellular process that generates the majority of the ATP of a cell through the electron-transfer chain, is highly dependent on proteins encoded by the mitochondrial genome (mtDNA). MtDNA replication is regulated by the nuclear-encoded mitochondrial transcription factor A (TFAM) and the mitochondrial-specific DNA polymerase gamma, which consists of a c...

BACKGROUND Fuchs endothelial corneal dystrophy (FECD) is a corneal disease characterized by abnormalities in the Descemet membrane and the corneal endothelium. The etiology of this disease is poorly understood. An increased level of oxidative DNA damage reported in FECD corneas suggests a role of DNA base excision repair (BER) genes in its pathogenesis. In this work, we searched for the associa...

OBJECTIVES Varicocele is associated with impaired testicular function and male infertility, but the molecular mechanisms by which fertility is affected have not been satisfactorily explained. The aim of our study was to investigate whether or not the polymerase gamma (POLG) polymorphism is associated with Iranian varicocele patients. MATERIALS AND METHODS We determined the POLG CAG repeat len...

Mitochondrial DNA damage is thought to be a causal contributor to aging as mice with inactivating mutations in polymerase gamma (Polg) develop a progeroid phenotype. To further understand the molecular mechanisms underlying this phenotype, we used iTRAQ and RNA-Seq to determine differences in protein and mRNA abundance respectively in the brains of one year old Polg mutator mice compared to con...

The maintenance of mitochondrial DNA (mtDNA) is dependent upon several nuclear gene-encoded proteins including enzymes forming the replisome needed to synthesise mtDNA. These need be present in balanced quantities function properly. In addition, mtDNA synthesis requires a supply nucleotides that achieved by nucleoside recycling inside mitochondria, and nucleotide import from cytosol. Mitochondr...