telomere maintenance via base-excision repair

Definition

Target type: biologicalprocess

A telomere maintenance process that occurs by base-excision repair of telomeric DNA in response to DNA damage. Telomeric sequences are particularly susceptible to oxidative DNA damage, due to their G-rich nature. [GOC:BHF, GOC:BHF_telomere, GOC:jbu, PMID:24703901]

Telomere maintenance via base-excision repair (BER) is a specialized pathway that counteracts the gradual shortening of telomeres that occurs with each cell division. Unlike the classic BER pathway, which primarily removes damaged bases from the genome, telomeric BER focuses on maintaining the integrity of the G-rich telomere overhang. Here's how it works:

1. **Recognition of Damage:** Telomeres are particularly susceptible to oxidative stress, which can lead to the formation of abasic sites (missing bases) within the G-rich overhang. These sites are recognized by specific DNA glycosylases, such as NEIL1 and OGG1, which remove the damaged base, leaving an abasic site.

2. **AP Endonuclease Activity:** The abasic site is then processed by an AP endonuclease, which cleaves the DNA backbone 5' to the abasic site. This creates a single-strand break with a 5' deoxyribose phosphate (dRP) group.

3. **dRP Removal and Gap Filling:** The dRP group is then removed by a specialized enzyme called dRP lyase, which is often part of the same protein as the AP endonuclease. This leaves a 3' hydroxyl group at the break site. The resulting gap is then filled in by DNA polymerase, using the complementary strand as a template.

4. **Ligase Action:** Finally, the nick is sealed by DNA ligase, restoring the integrity of the telomere.

This BER-mediated telomere maintenance pathway helps to preserve telomere length by efficiently repairing oxidative damage and preventing the accumulation of detrimental lesions. This mechanism is essential for maintaining genomic stability and cellular function.
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Proteins (1)

Compounds (17)