Clinical Presentation of Polymerase E1 (POLE1) and Polymerase E2 (POLE2) Deficiencies
The replicative DNA polymerases (pols) α, δ, and ɛ are central components in DNA replication, repair, recombination, and cell cycle control. Numerous genetic studies have provided compelling evidence to establish DNA polymerase ε (POLε/POLE) as the primary DNA polymerase responsible for leading strand synthesis during eukaryotic nuclear genome replication (Huang et al. 1999; Zahurancik et al. 2015). POLε is a highly conserved multi-subunit polymerase (heterotetramer) consisting of proteins encoded by four genes: POLE1, which encodes a 261 kDa protein comprising the catalytic activity complexed with the POLE2 (59 kDa) subunit, in addition to POLE3 (17 kDa) and POLE4 (12 kDa). POLE2 has no known catalytic activity, but the absence of POLE2 reduce Polε stability (Zahurancik et al. 2015). Polε is involved in several processes which include DNA replication, repair of DNA damage, control of cell cycle...
- Frugoni F, Dobbs K, Felgentreff K, Aldhekri H, Al Saud BK, Arnaout R, Ali AA, Abhyankar A, Alroqi F, Giliani S, Ojeda MM, Tsitsikov E, Pai SY, Casanova JL, Notarangelo LD, Manis JP. A novel mutation in the POLE2 gene causing combined immunodeficiency. J Allergy Clin Immunol. 2016;137: 635–8.e631.CrossRefGoogle Scholar
- Pachlopnik Schmid J, Lemoine R, Nehme N, Cormier-Daire V, Revy P, Debeurme F, Debre M, Nitschke P, Bole-Feysot C, Legeai-Mallet L, Lim A, De Villartay JP, Picard C, Durandy A, Fischer A, De Saint Basile G. Polymerase epsilon1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature (“FILS syndrome”). J Exp Med. 2012;209:2323–30.CrossRefGoogle Scholar
- Thiffault I, Saunders C, Jenkins J, Raje N, Canty K, Sharma M, Grote L, Welsh HI, Farrow E, Twist G, Miller N, Zwick D, Zellmer L, Kingsmore SF, Safina NP. A patient with polymerase E1 deficiency (POLE1): clinical features and overlap with DNA breakage/instability syndromes. BMC Med Genet. 2015;16:31.CrossRefGoogle Scholar