Fig. 2.

Resolution of persistent mitochondrial single strand breaks. A strand break with blocking groups at one or both exposed ends is unable to be repaired by simple SP-BER. The detection of these lesions may rely on more than one enzyme and potentially involves PARP, CSB or TFAM. The detection method may influence the type of lesion processing, either damage reversal, if a specific enzyme such as APTX or TDP1 are able to resolve the lesion, or damage excision, a more generic pathway that excises the DNA damage using the LP-BER pathway. In the mitochondria LP-BER dependant multi nucleotide excision appears to be driven by EXOG as part of an APE1 complex however the presence of FEN-1 and DNA2 in the mitochondria suggests a secondary LP-BER pathway, potentially to excise lesions resistant to EXOG activity. After the lesion has been resolved nucleotides are inserted by polymerase γ and the phosphodiester backbone re-ligated by ligase 3.