Helicase, POLQ-like, also known as hel308 and Holliday junction migration protein, encoded by the gene HEL308, is a DNA helicase found in humans, archea and many other organisms.[1] Its principal function is to allow DNA replication to continue past DNA forks.[2]
Like many proteins, Hel308 was named after a previously discovered protein to which it had some connection. In this case, the "Hel" stands for "human helicase" and the "308" is a reference to the Drosophila melanogaster protein Mus308, to which it is homologous.[5]
Classification
Hel308 is part of DNA helicase superfamily II, a group of enzymes that wind and unwind DNA.[1] Hel308 is found throughout archea and in some eukaryotes, including humans.[1][5] It contains twenty exons.[2]
Structure and function
Hel308's principal role is to repair replication-blocking lesions, such as interstrand DNA cross-links that interfere with the forking of DNA during replication.[1][5]
Hel308 is a large protein, 1101 amino acids in length,[3] with five separate domains. The third and fourth domains form a large central pore that holds single-stranded DNA. Its fifth domain acts as a brake by securing the single-strand DNA protruding through this pore.[6]
Clinical significance
Mutations in HEL308 are associated with cancer of the pharynx and mouth.[4]
↑ 3.03.1Marini F, Wood RD (Mar 2002). "A human DNA helicase homologous to the DNA cross-link sensitivity protein Mus308". The Journal of Biological Chemistry. 277 (10): 8716–23. doi:10.1074/jbc.M110271200. PMID11751861.
↑ 4.04.1Babron MC, Kazma R, Gaborieau V, McKay J, Brennan P, Sarasin A, Benhamou S (Jul 2014). "Genetic variants in DNA repair pathways and risk of upper aerodigestive tract cancers: combined analysis of data from two genome-wide association studies in European populations". Carcinogenesis. 35 (7): 1523–7. doi:10.1093/carcin/bgu075. PMID24658182.
↑ 5.05.15.25.3Woodman IL, Bolt EL (Jan 2011). "Winged helix domains with unknown function in Hel308 and related helicases". Biochemical Society Transactions. 39 (1): 140–4. doi:10.1042/BST0390140. PMID21265761.