exonuclease

An exonuclease is an enzyme that catalyzes the removal of nucleotides from the end of a polynucleotide chain. Unlike endonucleases, which cleave within the chain, exonucleases trim nucleotides one by one from an outer terminus. Exonucleases may operate in the 3' to 5' direction (removing nucleotides from the 3' end) or in the 5' to 3' direction (from the 5' end); some enzymes can act on both ends or on RNA as well as DNA.

Substrate preferences vary widely. Some exonucleases act on single-stranded nucleic acids, others on double-stranded molecules, and some preferentially target damaged or mismatched nucleotides to initiate repair.

In cellular DNA replication and repair, exonucleases contribute to genome maintenance. 3' to 5' proofreading exonuclease activity of DNA polymerases excises mispaired nucleotides during replication. Exonucleases also participate in base excision repair and mismatch repair by removing damaged or inappropriate nucleotides and creating suitable entry points for repair synthesis. They can also process DNA ends during homologous recombination and double-strand-break repair.

In RNA metabolism, exonucleases drive RNA turnover and quality control by degrading transcripts from their ends, shaping RNA lifetimes and abundance in the cell.

Exonucleases function as individual enzymes or as parts of larger complexes and often require divalent metal ions such as magnesium or manganese for catalysis. They are widely used in molecular biology to manipulate DNA and RNA ends, and defects in exonuclease activity can contribute to genomic instability and disease.