Dose dependent induction of mtDNA deletions by UVB irradiation of NHEK. NHEK cells were subjected to various doses of UVB radiation with an FS20 light source as indicated. Using primers ML3 and MR5 PCR products of 302 and 391 bp corresponding to the common deletion (CD) and a novel deletion (detailed in (ii) respectively are visible 24 hours after a 4 or 8 minute irradiation (1.43 mJ/cm²/min) with an FS20 light source.

mtDNA deletion cut sites. Mitochondrial nucleotide numbering according to the revised Cambridge reference sequence (HUMMTCG J01415.2 gi:113200490). Locations of cleavage sites in mitochondrial genomic sequences are indicated (▼ or ▲). Nucleotide repeats at or near the sites of cleavage are bracketed. In A, the placement of ▼ above the bracket indicates that the exact cleavage site within the nucleotide repeat is unknown. The joined ends in the deletion are indicated by ▽. The deletions in A are formed by cleavage within direct repeats. The deletion in iii is an imperfect repeat. Deletions formed by cleavage near, but not within, repeats are shown in B; nearby repeats adjacent to the cut sites are bracketed. The box in the deletion in C(i) shows a dinucleotide insertion. The primer pairs () used to generate the various PCR products are: A(i):ML2/MR1, A(ii):ML4/MR3, A(iii):ML6/MT3, B(i):MT1A/MT2, B(ii):MT1A/MT3, B(iii):ML4/MT3, C(i):MT1A/MT2, C(ii):ML3/MR5

A strand switching scheme for the formation of the deletion shown in . Irradiation produces a single strand nick between the upstream (5′) and downstream (3′) repeats. (1) Degradation of the nicked strand by the action of 3′ -> 5′ exonuclease past the 5′ repeat produces a single stranded segment containing the complementary 5′ repeat (). (2) Slipstrand base pairing between the 5′ and 3′ repeats. Since the repeats are inverted strands would be aligned in parallel in a triple helical configuration. (3) A hairpin is formed during DNA replication that is initiated from the recessed 3′ end. (4) Asymmetric resolution of the hairpin (the cleavage site is indicated by the arrowhead) followed by DNA replication during which template strands are switched (5) to produce an mtDNA that contains both the deletion and the nucleotide insertions (6).

Frequency analysis of mitochondrial DNA deletions in the database. Mitochondrial DNA deletions tabulated on the Mitomap website database were categorized according to the length of the nucleotide repeats at the deletion cut site.