POLA1 Gene

The POLA1 gene (POLA1 stands for "DNA polymerase alpha 1, catalytic subunit") is a protein-coding gene with the cytogenetic assignment: Xp22.11-p21.3.

The POLA1 gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two other primase subunits forms the DNA polymerase alpha complex. This enzyme complex, which occurs in eukaryotes, is involved in the initiation of DNA replication. The DNA polymerase alpha complex consists of 4 subunits: the catalytic subunit POLA1, the regulatory subunit POLA2 and the small and large primase subunits PRIM1 and PRIM2 respectively. As soon as the primase has produced the RNA primer, Pol alpha starts replication and extends the primer by about 20 nucleotides. The catalytic subunit POLA1 thus plays an essential role in the initiation of DNA replication.

Diseases associated with POLA1 include:

• Van Esch-O'Driscoll syndrome (Van Esch-O'Driscoll syndrome (VEODS) is characterized by varying degrees of intellectual disability, moderate to severe short stature, microcephaly, hypogonadism and various congenital malformations (Van Esch et al. 2019).

and

• X-linked reticular pigmentary disorder with systemic manifestations.

1. Ades LC et al (1993) An X-linked reticulate pigmentary disorder with systemic manifestations: report of a second family. Pediat Derm 10: 344-351.
2. Anderson RC et al (2005) X-linked reticulate pigmentary disorder with systemic manifestations: report of a third family and literature review. Pediat. Derm. 22: 122-126.
3. Partington MW et al (1989) Familial cutaneous amyloidosis with systemic manifestations in males. Am J Med Genet 10: 65-75.
4. Partington MW et al (1989) X-linked cutaneous amyloidosis: further clinical and pathological observations. Am J Med Genet 32: 115-119.
5. Starokadomskyy P et al (2016) DNA polymerase-alpha regulates the activation of type I interferons through cytosolic RNA:DNA synthesis. Nature Immun 17: 495-504.
6. Starokadomskyy P et al (2019) NK cell defects in X-linked pigmentary reticulum disorder. JCI Insight 4:e125688.
7. Van Esch H et al. (2019) Defective DNA polymerase alpha-primase leads to X-linked intellectual disability associated with severe growth retardation, microcephaly, and hypogonadism. Am. J. Hum. Genet104: 957-967-.