Pathway · 3 proteins
Joining and end processing
Ligases and nucleases process discontinuities and DNA ends.
How it works
- Two ligases are annotated: an NAD-dependent LigA and an ATP-dependent DNA ligase, which seal single-strand breaks using different cofactor chemistries.
- Several 3'-5' exonuclease and polymerase/exonuclease proteins, including a PolX-family enzyme, process mismatched or damaged ends before ligation.
- Which ligase handles which intermediate — a replication nick or a repair product — is not stated by the annotation, and the two families have overlapping but distinct roles in the literature.
Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.
Its proteins
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| DNA polymerase I | 2.7.7.7 | DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate | — | 574 | Step named |
| DNA ligase | 6.5.1.2 | NAD(+) + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + beta-nicotinamide D-nucleotide. | Zn(2+), Mn(2+), Mg(2+) | 720 | Step named |
| DNA polymerase III subunit epsilon | 2.7.7.7 | DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate | Mg(2+), Mn(2+) | 202 | Step named |
Also part of this pathway
These proteins are described under another pathway, but also take part here.
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| DNA-directed DNA polymeraseHome: DNA damage repair | 2.7.7.7 | DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate | — | 581 | Step named |
Origins
How could DNA and RNA strands be joined before ligases existed?
Ligase ribozymes have been isolated in the laboratory using several kinds of activated ends. One, from the Szostak group, uses an end activated with AMP, the same intermediate that the T4 DNA ligase uses.
Activating the end of a strand with three phosphates is difficult for prebiotic chemistry, so the experiments supply ends activated in other ways chosen by the researchers.
In the cell, joining DNA needs a ligase and an energy carrier, ATP or NAD, every time a gap is sealed during copying or repair.
From the books: Ribas de Pouplana (ed.), The Genetic Code and the Origin of Life, p. 55; Solomon, Berg & Martin, Biology, PDF p. 310.
The wider question for this part of the cell: origins for copying and repairing the genome.
Sources
- Atlas pathway grouping from the VF5 reference-genome system map (Deckert et al. 1998; Braakman & Smith 2014)
Other pathways in this group: DNA damage repair · DNA synthesis · Topology management · Recombination and restart · Chromosome preparation · Initiation and opening · Homologous recombination · Base excision repair · Cysteine and methionine metabolism · Not yet placed in a pathway