nucleotide-excision repair involved in interstrand cross-link repair

Definition

Target type: biologicalprocess

Any nucleotide-excision repair that is involved in interstrand cross-link repair. [GOC:TermGenie, PMID:22064477]

Nucleotide-excision repair (NER) is a major DNA repair pathway that removes a wide range of bulky DNA lesions, including interstrand cross-links (ICLs). ICLs are covalent bonds between two opposing DNA strands, which pose a significant threat to genome integrity and cell survival. NER is crucial for repairing ICLs and involves a complex series of steps:

1. **ICL Recognition and Unwinding:** ICLs are initially recognized by various DNA damage sensors and signaling proteins. These proteins trigger the recruitment of the Fanconi anemia (FA) pathway, which is essential for ICL repair. The FA pathway leads to the monoubiquitination of FANCD2, a key protein in ICL repair.

2. **Double Incision and ICL Removal:** After ICL recognition, the DNA is unwound by helicases. A specialized DNA endonuclease, known as ERCC1-XPF, makes a double incision flanking the ICL lesion, removing a segment of DNA containing the cross-link.

3. **Gap Filling and Ligation:** The excised region is then filled in by DNA polymerase using the intact strand as a template. Finally, the gap is sealed by DNA ligase, restoring the original DNA sequence.

4. **Translesion Synthesis (TLS):** In some cases, NER may be followed by TLS, where specialized DNA polymerases bypass the remaining damage. These polymerases are less accurate but can replicate through damaged DNA, allowing cells to continue replicating their genomes.

**NER is an intricate process involving numerous proteins and steps. Its proper functioning is essential for maintaining genomic stability and preventing the accumulation of DNA damage, which can lead to various diseases including cancer.**'
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Proteins (1)

Compounds (2)