LIG3
Domain
The PARP-type zinc finger is required for DNA ligase activity.
Function
Isoform 3 functions as a heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. Isoform 1 is targeted to mitochondria, where it functions as a DNA ligase in mitochondrial base-excision DNA repair (PubMed:10207110, PubMed:24674627).
Involvement in disease
Mitochondrial DNA depletion syndrome 20, MNGIE type
MTDPS20
An autosomal recessive mitochondrial disorder characterized by severe gut dysmotility, muscle weakness and atrophy, neurological abnormalities including epilepsy, migraine, stroke-like episodes, learning difficulties or cognitive decline, and neurogenic bladder. Brain imaging usually shows diffuse leukoencephalopathy and may show cerebellar atrophy. Disease onset can range from infancy to the teenage years.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the ATP-dependent DNA ligase family.
Tissue Specificity
Testis, thymus, prostate and heart.
Cellular localization
- Isoform 1
- Mitochondrion
- Contains an N-terminal mitochondrial transit peptide.
- Isoform 2
- Mitochondrion
- Contains an N-terminal mitochondrial transit peptide.
- Isoform 3
- Nucleus
- Lacks the N-terminal mitochondrial transit peptide.
- Isoform 4
- Nucleus
- Lacks the N-terminal mitochondrial transit peptide.
Alternative names
DNA ligase 3, DNA ligase III, Polydeoxyribonucleotide synthase [ATP] 3, LIG3