Mutant p53 cooperates with ETS2 to promote etoposide resistance.

Mutant p53 (mtp53) promotes chemotherapy resistance through multiple mechanisms, including disabling proapoptotic proteins and regulating gene expression. Comparison of genome wide analysis of mtp53 binding revealed that the ETS-binding site motif (EBS) is prevalent within predicted mtp53-binding sites. We demonstrate that mtp53 regulates gene expression through EBS in promoters and that ETS2 mediates the interaction with this motif.

Co-segregation and heteroplasmy of two coding-region mtDNA mutations within a matrilineal pedigree.

The ENG1 Leber's hereditary optic neuropathy (LHON) family spans six generations and comprises more than 90 maternally related individuals. In this pedigree, the G:A LHON mutation at nucleotide position 11778 shows a complex pattern of segregation in which it is homoplasmic mutant in two branches, homoplasmic wildtype in another, and heteroplasmic in a fourth branch. In addition, there is co-segregation of the 11778 mutant allele and of a G:A silent polymorphism at nucleotide position 5471 in 18 of 19 family members.

Lightning strikes twice: Leber hereditary optic neuropathy families with two pathogenic mtDNA mutations.

Objective: To report the clinical and mitochondrial genetic analyses of two families, each of which carries both the 11778 and 14484 Leber hereditary optic neuropathy (LHON) mutations in mitochondrial DNA.

Methods: In addition to detailed clinical histories, the complete sequence of the mitochondrial DNA (mtDNA) from each family was determined.

Results: A small Australian LHON family (Vic20) and a family from the United States carry the 11778 and 14484 LHON mutations.

A high frequency of mtDNA polymorphisms in HeLa cell sublines.

The complete mtDNA sequences from the uncloned "founder" HeLa cells and from five sublines have been determined. These sequences all carry a common "core" of 38 single basepair alterations relative to the revised Cambridge Reference Sequence (CRS). The HeLa mitochondrial genome is of African descent and it is a member of the African L3 haplogroup.