title: Two copies of mthmg1, encoding a novel mitochondrial HMG-like protein, delay accumulation of mitochondrial DNA deletions in Podospora anserina.
abstract: In the filamentous fungus Podospora anserina, two degenerative processes which result in growth arrest are associated with mitochondrial genome (mitochondrial DNA [mtDNA]) instability. Senescence is correlated with mtDNA rearrangements and amplification of specific regions (senDNAs). Premature death syndrome is characterized by the accumulation of specific mtDNA deletions. This accumulation is due to indirect effects of the AS1-4 mutation, which alters a cytosolic ribosomal protein gene. The mthmg1 gene has been identified as a double-copy suppressor of premature death. It greatly delays premature death and the accumulation of deletions when it is present in two copies in an ASI-4 context. The duplication of mthmg1 has no significant effect on the wild-type life span or on senDNA patterns. In anAS1+ context, deletion of the mthmg1 gene alters germination, growth, and fertility and reduces the life span. The deltamthmg1 senescent strains display a particular senDNA pattern. This deletion is lethal in an AS1-4 context. According to its physical properties (very basic protein with putative mitochondrial targeting sequence and HMG-type DNA-binding domains) and the cellular localization of an mtHMG1-green fluorescent protein fusion, mtHMG1 appears to be a mitochondrial protein possibly associated with mtDNA. It is noteworthy that it is the first example of a protein combining the two DNA-binding domains, AT-hook motif and HMG-1 boxes. It may be involved in the stability and/or transmission of the mitochondrial genome. To date, no structural homologues have been found in other organisms. However, mtHMG1 displays functional similarities with the Saccharomyces cerevisiae mitochondrial HMG-box protein Abf2.
authors.affiliation: Institut de Génétique et Microbiologie, CNRS UMR 8621, Bâtiment 400, Université Paris-Sud, 91405 Orsay Cedex, France. chablat@igmors.u-psud.fr
authors.forename: Michelle
authors.initials: M
authors.lastname: Dequard-Chablat
authors.forename: Cynthia
authors.initials: C
authors.lastname: Allandt
mesh_terms: D000595:Amino Acid Sequence; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D018628:Gene Dosage; D005800:Genes, Fungal; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D015183:Restriction Mapping; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D020037:Sordariales / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D005656:Fungal Proteins; D024243:HMGB1 Protein; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins