5'-flap endonuclease activity

Definition

Target type: molecularfunction

Catalysis of the cleavage of a 5' flap structure in DNA, but not other DNA structures; processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. [PMID:9778254]

5'-flap endonuclease activity is a specialized enzymatic function involved in DNA metabolism, particularly during DNA replication and repair. It specifically cleaves the phosphodiester bond at the 5' end of a DNA flap structure, a single-stranded DNA segment that is displaced from a double-stranded DNA molecule. This activity is essential for removing unwanted or damaged DNA sequences during replication and repair, ensuring the integrity of the genome. The 5' flap structure can arise in various contexts, including:

- **Okazaki fragment processing:** During lagging strand synthesis in DNA replication, short DNA fragments called Okazaki fragments are synthesized discontinuously. These fragments need to be joined together, and 5'-flap endonuclease activity is crucial for removing the 5' flaps generated during the ligation process.

- **Base excision repair (BER):** In BER, damaged DNA bases are removed, creating a gap in the DNA strand. The gap is then filled by DNA polymerase, but the newly synthesized strand might have a 5' flap. 5'-flap endonuclease activity helps to remove this flap, ensuring the integrity of the repaired DNA sequence.

- **Nucleotide excision repair (NER):** NER is a major repair pathway for bulky DNA lesions, such as those caused by UV radiation. This pathway involves removing the damaged segment, leaving a gap that is filled by DNA polymerase. 5'-flap endonuclease activity is often involved in removing the 5' flap generated during NER.

- **Recombination:** During homologous recombination, two DNA molecules exchange genetic information. This process involves the formation of Holliday junctions, which can be resolved by 5'-flap endonuclease activity.

The enzymatic mechanism of 5'-flap endonuclease activity involves the recognition and binding of the 5' flap structure, followed by the cleavage of the phosphodiester bond. This activity is often associated with other enzymatic functions, such as DNA polymerase activity or exonuclease activity, within multi-functional enzymes.

Overall, 5'-flap endonuclease activity plays a crucial role in maintaining genome stability by ensuring accurate DNA replication and efficient repair of DNA damage. This activity is essential for cellular survival and prevents the accumulation of mutations that can lead to various diseases.'
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Proteins (2)

Compounds (3)