DNA Modifying Enzymes

Eukaryotic and prokaryotic cells possess multiple mechanisms to repair DNA and control damage to their genomes. These include base excision repair (BER) and nucleotide excision repair (NER) that excise and replace damaged nucleotide bases and helix-distorting lesions, respectively. Many of the enzymes involved in NER are also active in transcription-coupled repair (TCR) processes. In addition, mismatch repair (MMR) enzymes act to replace mismatched nucleotides and repair insertion/deletion loops. Furthermore, there are two types of double-stranded DNA break repair, homologous recombination (HR) and non-homologous end-joining (NHEJ).

Base excision repair proteins correct DNA lesions and ensure that mutations are not propagated. The process of base excision repair is achieved via specific and sequential enzyme activity. Damaged bases are first identified and removed by DNA glycosylases/AP lyases, which break beta-N glycosidic bonds to create an abasic (AP) DNA site. Depending on the initial events of base removal, repair proceeds through either the short patch (1 nucleotide) or long patch (2-10 nucleotides) repair pathways. This involves the AP site being recognized by endonuclease enzymes which nick the damaged DNA, and recruit DNA polymerases to fill the gap in the DNA. Base excision repair is completed by DNA ligase sealing the nick between the two strands.

Nucleotide excision is an additional DNA repair mechanism which removes nucleotides that have been damaged by chemicals or ultraviolet radiation. Nucleotide excision generates a short single-stranded DNA gap, which is subsequently used as a template by DNA polymerase. In addition to base and nucleotide excision repair molecules, mismatch repair (MMR) enzymes act to replace mismatched nucleotides and repair insertion/deletion loops. Genotoxic stress can introduce DNA double-strand breaks (DSBs), which are repaired by either homologous recombination or non-homologous end-joining. The Mre11/Rad50/Nbs1 (MRN) complex, along with members of the Rad51 family of proteins, are involved in double-strand break repair during homologous recombination. R&D Systems offers quality DNA enzyme products which include DNA glycosidases, endonucleases, polymerases, ligases, and more.