Nucleotide excision repair (NER) is a critical DNA repair pathway that removes a wide range of DNA lesions, including those caused by UV light and chemical agents. The process involves a complex network of proteins that recognize and remove damaged DNA, ensuring genomic stability. Key components of NER include XPC-hHR23B, which acts as a DNA damage sensor and recruits other repair factors. TFIIH, a multi-subunit complex, is essential for unwinding DNA at the lesion site and is involved in both global genome NER (GG-NER) and transcription-coupled NER (TC-NER). XPA verifies the damage and helps assemble the repair machinery, while RPA stabilizes the opened DNA and positions endonucleases for incision. XPG and ERCC1-XPF make the 3' and 5' incisions, respectively, and are crucial for the dual incision step. The repair process involves the removal of the damaged segment, followed by DNA synthesis and ligation. NER is also linked to various syndromes, such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS), which highlight the importance of NER in maintaining genomic integrity. Recent studies have elucidated the molecular mechanisms of NER, including the roles of various proteins in damage recognition, complex formation, and repair synthesis. The interplay between NER and other repair pathways, such as base excision repair (BER) and mismatch repair, underscores the complexity of DNA repair mechanisms in cells. Understanding these processes is essential for developing therapeutic strategies for diseases associated with NER defects.Nucleotide excision repair (NER) is a critical DNA repair pathway that removes a wide range of DNA lesions, including those caused by UV light and chemical agents. The process involves a complex network of proteins that recognize and remove damaged DNA, ensuring genomic stability. Key components of NER include XPC-hHR23B, which acts as a DNA damage sensor and recruits other repair factors. TFIIH, a multi-subunit complex, is essential for unwinding DNA at the lesion site and is involved in both global genome NER (GG-NER) and transcription-coupled NER (TC-NER). XPA verifies the damage and helps assemble the repair machinery, while RPA stabilizes the opened DNA and positions endonucleases for incision. XPG and ERCC1-XPF make the 3' and 5' incisions, respectively, and are crucial for the dual incision step. The repair process involves the removal of the damaged segment, followed by DNA synthesis and ligation. NER is also linked to various syndromes, such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS), which highlight the importance of NER in maintaining genomic integrity. Recent studies have elucidated the molecular mechanisms of NER, including the roles of various proteins in damage recognition, complex formation, and repair synthesis. The interplay between NER and other repair pathways, such as base excision repair (BER) and mismatch repair, underscores the complexity of DNA repair mechanisms in cells. Understanding these processes is essential for developing therapeutic strategies for diseases associated with NER defects.