TOP3A

TOP3A (Topoisomerase (DNA) III alpha) is a protein that in humans is encoded by the TOP3A gene. This enzyme is part of the topoisomerase family, which plays a critical role in DNA replication, transcription, recombination, and chromosome segregation. Topoisomerases work by transiently breaking and rejoining DNA strands to relieve the torsional stress that builds up during various cellular processes.

The TOP3A gene is located on chromosome 17q21.31 and consists of 23 exons. The protein encoded by this gene is a type IA topoisomerase, which can relax negative but not positive supercoiled DNA. Unlike other topoisomerases, TOP3A has a unique function in DNA decatenation (untangling DNA molecules) during the end of DNA replication and is also involved in the regulation of gene expression and maintenance of genomic stability.

In addition to its role in DNA replication and repair, TOP3A interacts with several other proteins, including Bloom syndrome protein (BLM) and RecQ protein-like 4 (RECQL4), forming a complex that is essential for the proper processing of recombination intermediates and preventing genomic instability. Mutations in the TOP3A gene or dysregulation of its expression have been associated with various forms of cancer, highlighting its importance in maintaining genomic integrity.

Function

TOP3A serves several critical functions in the cell:

• It resolves topological stress during DNA replication and transcription.
• It plays a key role in the dissolution of Holliday junctions, a type of recombination intermediate.
• It works in conjunction with BLM and RECQL4 to prevent genomic instability by resolving DNA structures that can lead to chromosome breakage and rearrangement.

Clinical Significance

Alterations in TOP3A expression or mutations can lead to genomic instability, which is a hallmark of cancer. Studies have shown that TOP3A is involved in various cancers, including breast cancer, ovarian cancer, and colorectal cancer. Understanding the mechanisms by which TOP3A maintains genomic stability may provide insights into cancer development and lead to potential therapeutic targets.

See Also

• Topoisomerase
• DNA replication
• Genomic instability
• Bloom syndrome