Cell complexity: how mitochondria maintain DNA (Introduction)

by David Turell , Friday, May 11, 2018, 18:19 (2175 days ago) @ David Turell

The DNA in mitochondria differs from that in the nucleus. It has a circular form:

https://phys.org/news/2018-05-mitochondria-art-dna-maintenance.html

"However, biologists also know that most of our cells have mitochondria that do, in fact, retain the circular DNA, the chromosome 'M,' which they inherited from their prokaryotic ancestors.

"One might then ask: Do mitochondria contain linear DNA? The correct answer to this second, and somewhat sneaky question is, again, affirmative. Nucleoids in mitochondria do need to be circular in order for the machinery that copies their DNA to work. Transcription in mitochondria is directly coupled to replication, and also requires circularized nucleoids. However, linear nucleoids exist in a healthy state of equilibrium with circular nucleoids within the mitochondria network. This provides a way for the cell or tissue to control the abundance of mtDNA directly, and by implication, the state and abundance of mitochondria.

"What is the fate of linear mtDNA? Double-strand breaks (DSBs) are continually generated as a byproduct of replication stalling, or from failed DNA repair of damaged and incorrectly replicated nucleotides. Although nucleoids can normally replicate themselves in about 90 minutes, DNA polymerases are hung out to dry when nucleotide stores are insufficient or become improperly balanced. When that happens, things break down; essential factors begin to leave the replication-transcription complex, and proper proofreading becomes a frequent casualty.

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"Until recently, it was not understood how linear mtDNA was degraded. Authors of a new paper in Nature have now shown that the same exact machinery responsible for replicating mtDNA also polices it for breaks. The three main proteins involved, the helicase TWNK, the polymerase POLG, and the exonuclease MGME1, were found to bind together into a functional unit. TWNK first acts to unwind the DNA so that the individual strands can be accessed. MGME1, which has a strong bias for operation in the 5' to 3' direction of single-stranded DNA then begins to digest one strand.

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"Some additional insights (and warnings) into how double-strand breaks might occur and resolve have been provided by researchers Doug Turnbill and Robert Taylor from the Wellcome Center for Mitochondrial Research. In one particular paper, they proposed that mtDNA deletions are most commonly generated during repair of DNA damage as opposed to replication errors. More specifically, they offer that characteristic deletions are initiated by single-stranded segments of mtDNA that were, in turn, generated by exonucleases attacking double-strand breaks. The free single strands would be able to anneal with microhomology or repeat sequences on other single-stranded mtDNA, and undergo repair to an intact but partially deleted state."

Comment: Obviously the cell and its mitochonria must have exacting repair mechanisms, and these must have been present from the beginning of life and carried into multcellularity. Only design explains this.