Helicase, POLQ-like

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.[5]

HELQ
Identifiers
AliasesHELQ, HEL308, helicase, POLQ-like, helicase, POLQ like
External IDsOMIM: 606769 MGI: 2176740 HomoloGene: 14667 GeneCards: HELQ
Orthologs
SpeciesHumanMouse
Entrez

113510

191578

Ensembl

ENSG00000163312

ENSMUSG00000035266

UniProt

Q8TDG4

Q2VPA6

RefSeq (mRNA)

NM_001081107
NM_180984

RefSeq (protein)

NP_001074576

Location (UCSC)Chr 4: 83.41 – 83.46 MbChr 5: 100.91 – 100.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

The gene encoding this enzyme, HELQ1, is located on chromosome 4q21 in humans.[6] It is associated with the polymerase pathway.[7]

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.[8]

Classification

Hel308 is part of DNA helicase superfamily II, a group of enzymes that wind and unwind DNA.[5] Hel308 is found throughout archea and in some eukaryotes, including humans.[5][8] It contains twenty exons.[9]

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.[10][11] 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.[12] 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.[5][8][13]

Hel308 is a large protein, 1101 amino acids in length,[6] 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.[14]

Clinical significance

Mutations in HEL308 are associated with cancer of the pharynx and mouth.[7]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000163312 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000035266 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Tafel AA, Wu L, McHugh PJ (May 2011). "Human HEL308 localizes to damaged replication forks and unwinds lagging strand structures". The Journal of Biological Chemistry. 286 (18): 15832–15840. doi:10.1074/jbc.M111.228189. PMC 3091193. PMID 21398521.
  6. Marini F, Wood RD (March 2002). "A human DNA helicase homologous to the DNA cross-link sensitivity protein Mus308". The Journal of Biological Chemistry. 277 (10): 8716–8723. doi:10.1074/jbc.M110271200. PMID 11751861.
  7. Babron MC, Kazma R, Gaborieau V, McKay J, Brennan P, Sarasin A, Benhamou S (July 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): 1523–1527. doi:10.1093/carcin/bgu075. PMID 24658182.
  8. Woodman IL, Bolt EL (January 2011). "Winged helix domains with unknown function in Hel308 and related helicases". Biochemical Society Transactions. 39 (1): 140–144. doi:10.1042/BST0390140. PMID 21265761.
  9. "HELQ helicase, POLQ-like [ Homo sapiens (human) ]". NCBI. National Institutes of Health. February 21, 2016.
  10. Kamp JA, Lemmens BB, Romeijn RJ, Changoer SC, van Schendel R, Tijsterman M (December 2021). "Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications". Nature Communications. 12 (1): 7126. Bibcode:2021NatCo..12.7126K. doi:10.1038/s41467-021-27408-z. PMC 8654963. PMID 34880204.
  11. Anand R, Buechelmaier E, Belan O, Newton M, Vancevska A, Kaczmarczyk A, et al. (December 2021). "HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51". Nature. 601 (7892): 268–273. doi:10.1038/s41586-021-04261-0. PMC 8755542. PMID 34937945.
  12. Kamp JA, Lemmens BB, Romeijn RJ, Changoer SC, van Schendel R, Tijsterman M (December 2021). "Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications". Nature Communications. 12 (1): 7126. Bibcode:2021NatCo..12.7126K. doi:10.1038/s41467-021-27408-z. PMC 8654963. PMID 34880204.
  13. Muzzini DM, Plevani P, Boulton SJ, Cassata G, Marini F (June 2008). "Caenorhabditis elegans POLQ-1 and HEL-308 function in two distinct DNA interstrand cross-link repair pathways". DNA Repair. 7 (6): 941–950. doi:10.1016/j.dnarep.2008.03.021. PMID 18472307.
  14. Richards JD, Johnson KA, Liu H, McRobbie AM, McMahon S, Oke M, et al. (February 2008). "Structure of the DNA repair helicase hel308 reveals DNA binding and autoinhibitory domains". The Journal of Biological Chemistry. 283 (8): 5118–5126. doi:10.1074/jbc.M707548200. PMC 3434800. PMID 18056710.
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