Excision repair mechanism

Excision repair mechanism is a critical process in cell biology and genetics that involves the removal and subsequent repair of damaged DNA to maintain genetic stability and prevent mutations that could lead to diseases such as cancer. This article delves into the types, mechanisms, and significance of excision repair in cellular function.

Types of Excision Repair

There are primarily two types of excision repair: Nucleotide Excision Repair (NER) and Base Excision Repair (BER).

Nucleotide Excision Repair (NER)

NER is a mechanism that removes bulky, helix-distorting damage such as thymine dimers, which are often caused by ultraviolet (UV) radiation. NER operates through a multi-step process involving damage recognition, excision of a short single-stranded DNA segment containing the lesion, and synthesis of a replacement strand using the undamaged strand as a template.

Base Excision Repair (BER)

BER addresses small, non-helix-distorting base lesions caused by oxidative stress, alkylation, or deamination. This process involves the recognition and removal of the damaged base by a specific DNA glycosylase, followed by end processing, gap filling by a DNA polymerase, and DNA ligase-mediated sealing of the nick.

Mechanism

The excision repair mechanisms share a general strategy but differ in the specifics of lesion recognition and repair synthesis.

NER Mechanism

1. Damage Recognition: Complexes such as the XPC protein or the UV-DDB complex recognize the DNA damage. 2. Recruitment of Repair Factors: The TFIIH complex, with its helicase activity, unwinds the DNA around the damage, allowing other factors to access the lesion. 3. Excision of Damaged DNA: Endonucleases make incisions on both sides of the lesion, and a short single-stranded DNA segment containing the damage is removed. 4. Repair Synthesis: DNA polymerase fills in the gap using the undamaged strand as a template. 5. Ligation: DNA ligase seals the remaining nick, restoring the DNA to its original state.

BER Mechanism

1. Damage Recognition: A specific DNA glycosylase recognizes and removes the damaged base, creating an abasic site. 2. End Processing: An endonuclease, APE1, makes a nick in the phosphodiester backbone near the abasic site. 3. Gap Filling: DNA polymerase inserts the correct nucleotide into the gap. 4. Ligation: DNA ligase seals the nick, completing the repair process.

Significance

The excision repair mechanisms are vital for maintaining genomic integrity. By correcting DNA damage, they prevent mutations that could lead to genetic disorders and cancer. Furthermore, these mechanisms play a role in the aging process and the cellular response to environmental stresses.