Biology:Helicase, POLQ-like
 Generic protein structure example |
Helicase, POLQ-like, also known as helicase Q, hel308 and Holliday junction migration protein, encoded by the gene HELQ1, is a DNA helicase found in humans, archea and many other organisms.[1]
Gene
The gene encoding this enzyme, HELQ1, is located on chromosome 4q21 in humans.[2] It is associated with the polymerase pathway.[3]
Nomenclature
When first reported, Helicase Q was called "Holliday junction migration protein."
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.[4]
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][4] It contains twenty exons.[5]
Structure and function
Helicase Q's principal role is in the DNA repair. Helicase Q was shown to play a role in the repair of DNA double-strand breaks and to prevent tandem duplications.[6][7] More specifically, it plays a role in multiple pathways where stretches of homologous nucleotides are annealed, like microhomology-mediated end-joining and single-strand annealing.[8] Organisms with mutations in the gene encoding helicase Q are sensitive to replication-blocking lesions, such as interstrand DNA cross-links that interfere with the forking of DNA during replication.[1][4][9]
Hel308 is a large protein, 1101 amino acids in length,[2] 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.[10]
Clinical significance
Mutations in HEL308 are associated with cancer of the pharynx and mouth.[3]
See also
References
- ↑ 1.0 1.1 1.2 1.3 "Human HEL308 localizes to damaged replication forks and unwinds lagging strand structures". The Journal of Biological Chemistry 286 (18): 15832–15840. May 2011. doi:10.1074/jbc.M111.228189. PMID 21398521.
- ↑ 2.0 2.1 "A human DNA helicase homologous to the DNA cross-link sensitivity protein Mus308". The Journal of Biological Chemistry 277 (10): 8716–8723. March 2002. doi:10.1074/jbc.M110271200. PMID 11751861.
- ↑ 3.0 3.1 "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): 1523–1527. July 2014. doi:10.1093/carcin/bgu075. PMID 24658182.
- ↑ 4.0 4.1 4.2 "Winged helix domains with unknown function in Hel308 and related helicases". Biochemical Society Transactions 39 (1): 140–144. January 2011. doi:10.1042/BST0390140. PMID 21265761.
- ↑ "HELQ helicase, POLQ-like [ Homo sapiens (human) "]. National Institutes of Health. February 21, 2016. https://www.ncbi.nlm.nih.gov/gene/113510.
- ↑ "Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications". Nature Communications 12 (1): 7126. December 2021. doi:10.1038/s41467-021-27408-z. PMID 34880204. Bibcode: 2021NatCo..12.7126K.
- ↑ "HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51". Nature 601 (7892): 268–273. December 2021. doi:10.1038/s41586-021-04261-0. PMID 34937945.
- ↑ "Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications". Nature Communications 12 (1): 7126. December 2021. doi:10.1038/s41467-021-27408-z. PMID 34880204. Bibcode: 2021NatCo..12.7126K.
- ↑ "Caenorhabditis elegans POLQ-1 and HEL-308 function in two distinct DNA interstrand cross-link repair pathways". DNA Repair 7 (6): 941–950. June 2008. doi:10.1016/j.dnarep.2008.03.021. PMID 18472307.
- ↑ "Structure of the DNA repair helicase hel308 reveals DNA binding and autoinhibitory domains". The Journal of Biological Chemistry 283 (8): 5118–5126. February 2008. doi:10.1074/jbc.M707548200. PMID 18056710.
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