LIG4
DNA ligase 1 (LIG1) is an essential enzyme in humans that plays a critical role in DNA replication and DNA repair. It is encoded by the LIG1 gene located on chromosome 19q13.33. DNA ligase 1 is responsible for joining Okazaki fragments on the lagging strand during DNA replication and for sealing nicks in the DNA during various repair processes.
Structure[edit | edit source]
DNA ligase 1 is a member of the ATP-dependent DNA ligase family. The enzyme consists of several domains, including a DNA-binding domain, an adenylation domain, and an OB-fold domain. These domains work together to facilitate the ligation process, which involves the formation of a phosphodiester bond between adjacent nucleotides.
Function[edit | edit source]
DNA ligase 1 is primarily involved in the following cellular processes:
DNA Replication[edit | edit source]
During DNA replication, the lagging strand is synthesized in short segments known as Okazaki fragments. DNA ligase 1 is responsible for joining these fragments to form a continuous DNA strand. This process is crucial for maintaining the integrity of the genetic material during cell division.
DNA Repair[edit | edit source]
DNA ligase 1 also plays a vital role in various DNA repair pathways, including base excision repair (BER) and nucleotide excision repair (NER). In these pathways, DNA ligase 1 seals nicks in the DNA backbone that arise during the repair of damaged or mismatched bases.
Clinical Significance[edit | edit source]
Mutations in the LIG1 gene can lead to a rare genetic disorder known as DNA ligase I deficiency. This condition is characterized by immunodeficiency, growth retardation, and increased sensitivity to DNA-damaging agents. Understanding the function and regulation of DNA ligase 1 is important for developing therapeutic strategies for diseases associated with DNA repair defects.
Research and Applications[edit | edit source]
DNA ligase 1 is a target for research in cancer therapy, as its activity is crucial for the survival of rapidly dividing cancer cells. Inhibitors of DNA ligase 1 are being investigated as potential chemotherapeutic agents.
Also see[edit | edit source]
| Excision repair | |
|---|---|
| Other forms of repair | |
| Other/ungrouped proteins | |
| Regulation | |
| Other/ungrouped | |
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Contributors: Prab R. Tumpati, MD
