POLA1

Description

The POLA1 (DNA polymerase alpha 1, catalytic subunit) is a protein-coding gene located on chromosome X.

POLA1 is a human gene encoding the p180 catalytic subunit of DNA polymerase α-primase, a key enzyme involved in DNA replication. It is responsible for initiating DNA synthesis at origins of replication on both leading and lagging strands, as well as during the synthesis of Okazaki fragments on the lagging strand. POLA1 functions within a complex consisting of four subunits: POLA1 itself, POLA2, PRIM1, and PRIM2. While POLA1 initiates replication, it lacks the processivity and proofreading ability necessary for efficient long-term DNA copying. Therefore, it hands off the replication process to polymerase delta and epsilon. POLA1 also plays a role in regulating type I interferon activation, which is involved in immune responses. A mutation in the POLA1 gene has been linked to X-linked reticulate pigmentary disorder (XLPDR).

The POLA1 protein is a catalytic subunit of the DNA polymerase alpha complex, also known as the alpha DNA polymerase-primase complex. This complex plays a critical role in initiating DNA synthesis. During the S phase of the cell cycle, the POLA1 complex, consisting of POLA1, POLA2, PRIM1, and PRIM2, is recruited to DNA at replication forks through interactions with MCM10 and WDHD1. The primase subunit within the complex initiates DNA synthesis by creating short RNA primers on both leading and lagging strands. These primers are then extended by the POLA1 subunit before being handed off to polymerase delta and epsilon for further, more processive synthesis on the lagging and leading strands, respectively. This transfer occurs because POLA1 has limited processivity and lacks proofreading capabilities, making it inefficient for replicating long DNA sequences. In the cytosol, POLA1 contributes significantly to the concentration of cytosolic RNA:DNA hybrids, essential for preventing spontaneous activation of type I interferon responses.

POLA1 is also known as NSX, PDR, POLA, VEODS, p180.

Associated Diseases

• X-linked intellectual disability, Van Esch type
• Van Esch-O'Driscoll syndrome
• Pigmentary disorder, reticulate, with systemic manifestations, X-linked