RNASEH1

RNASEH1 (Ribonuclease H1) is an enzyme that in humans is encoded by the RNASEH1 gene. This enzyme plays a crucial role in the metabolism of RNA molecules, specifically in the removal of RNA primers from DNA strands during DNA replication and in the repair and maintenance of DNA. RNASEH1 is part of the ribonuclease H family, which is characterized by its ability to cleave the RNA strand of RNA-DNA hybrids.

Function

RNASEH1 is essential for DNA replication and repair processes. During DNA replication, RNA primers are synthesized by primase and are necessary for DNA polymerases to initiate synthesis of the new DNA strand. Once the DNA strand is elongated, RNASEH1 removes the RNA primers, allowing DNA polymerases to fill in the gaps with DNA. This action is crucial for the accurate duplication of the genome and for maintaining the integrity of genetic information.

In addition to its role in DNA replication, RNASEH1 is involved in DNA repair mechanisms. It helps in the removal of ribonucleotides misincorporated into DNA and in the resolution of R-loops, structures that can lead to genomic instability if not properly managed.

Clinical Significance

Mutations in the RNASEH1 gene have been associated with various genetic disorders, including progressive external ophthalmoplegia (PEO), a condition characterized by weakness of the muscles around the eyes and other muscles involved in movement. These mutations can lead to a reduction in RNASEH1 activity, resulting in mitochondrial DNA deletions and, consequently, mitochondrial dysfunction.

Research has also suggested a potential role of RNASEH1 in cancer biology. Altered expression of RNASEH1 has been observed in certain types of cancer, indicating that it may contribute to cancer development and progression through its involvement in DNA repair and replication processes.

Structure

The RNASEH1 enzyme consists of several domains, including a catalytic domain that is responsible for its enzymatic activity. The structure of RNASEH1 is critical for its interaction with RNA-DNA hybrids and for the specificity of its enzymatic action.

Genetics

The RNASEH1 gene is located on chromosome 2 in humans. It encodes the RNASEH1 protein, which is expressed in various tissues throughout the body, reflecting its fundamental role in cellular processes.

See Also

• DNA replication
• DNA repair
• Mitochondrial DNA
• Progressive external ophthalmoplegia
• Ribonuclease H