Ku (protein)

Ku bound to DNA

Ku (protein) is a protein that plays a critical role in the repair of DNA double-strand breaks (DSBs), a type of DNA damage that can lead to cell death or cancer if not properly repaired. Ku is a heterodimer, meaning it is composed of two subunits, Ku70 and Ku80 (also known as Ku86), which bind to each other to form the active protein complex. This complex is a key component of the non-homologous end joining (NHEJ) pathway, a major mechanism for repairing DSBs in eukaryotic cells.

Function

The primary function of Ku is to recognize and bind to the ends of DSBs. Upon binding, Ku recruits other proteins involved in the NHEJ pathway, including the DNA-dependent protein kinase (DNA-PKcs), to the site of damage. This recruitment is essential for the proper alignment and ligation of the broken DNA ends, thereby restoring the integrity of the genome.

Ku also plays a role in other cellular processes, including telomere maintenance, transcription regulation, and apoptosis. Its involvement in these processes highlights the importance of Ku beyond DNA repair, implicating it in cellular aging, cancer, and the immune response.

Structure

Ku is characterized by its high affinity for DNA ends, a property conferred by its unique structure. The heterodimer forms a ring-like structure that can encircle DNA, providing a platform for the assembly of other NHEJ components. The interaction between Ku70 and Ku80 is highly specific and stable, making the Ku complex an efficient and effective responder to DNA damage.

Clinical Significance

Given its critical role in DNA repair, Ku has been implicated in several human diseases. Deficiencies in Ku function can lead to increased sensitivity to DNA-damaging agents, contributing to cancer susceptibility. Conversely, overexpression of Ku has been observed in certain types of cancer, suggesting a role in tumor progression and resistance to therapy.

In addition to cancer, alterations in Ku levels and function have been associated with autoimmune diseases and aging. The precise mechanisms by which Ku contributes to these conditions are an active area of research, with the potential to inform new therapeutic strategies.

Research and Applications

Research on Ku has led to advancements in our understanding of DNA repair mechanisms and their implications for health and disease. This knowledge has potential applications in the development of targeted cancer therapies, strategies for managing age-related diseases, and interventions to enhance genome stability.

See Also

• DNA repair
• Non-homologous end joining
• DNA damage
• Eukaryotic cells
• Cancer