RecQ helicase

protein
Name = Bloom syndrome
caption =


width =
HGNCid = 1058
Symbol = BLM
AltSymbols =
EntrezGene = 641
OMIM = 604610
RefSeq = NM_000057
UniProt = P54132
PDB =
ECnumber =
Chromosome = 15
Arm =
Band =
LocusSupplementaryData = protein
Name = RecQ protein-like 4
caption =


width =
HGNCid = 9949
Symbol = RECQL4
AltSymbols =
EntrezGene = 9401
OMIM = 603780
RefSeq = NM_004260
UniProt = O94761
PDB =
ECnumber =
Chromosome = 8
Arm = q
Band = 24.3
LocusSupplementaryData = protein
Name = Werner syndrome
caption =


width =
HGNCid = 12791
Symbol = WRN
AltSymbols =
EntrezGene = 7486
OMIM = 604611
RefSeq = NM_000553
UniProt = Q14191
PDB =
ECnumber =
Chromosome = 8
Arm = p
Band =
LocusSupplementaryData =

RecQ helicase is a family of helicase enzymes that has been shown to be important in genome maintenance. They function through unwinding paired DNA and translocating in the 3' to 5' direction.

In prokaryotes RecQ is necessary for plasmid recombination and DNA repair from UV-light induced DNA damage. In eukaryotes, replication does not proceed normally in the absence of RecQ proteins, which also function in aging, silencing, recombination and DNA repair.

RecQ family members share three regions of conserved protein sequence referred to as the Helicase, RecQ-conserved (RecQ-Ct) and Helicase-and-RNase-D-C-terminal (HRDC) domains. The removal of the N-terminal residues (Helicase and, RecQ-Ct domains) impairs both helicase and ATPase activity but has no effect on the binding ability of RecQ implying that the N-terminus functions as the catalytic end. Truncations of the C-terminus (HRDC domain) compromise the binding ability of RecQ but not the catalytic function. The importance of RecQ in cellular functions is exemplified by human diseases, which all lead to genomic instability and a predisposition to cancer.

There are at least five human RecQ genes; and mutations in any of the three human RecQ genes are implicated in heritable human diseases: WRN gene in Werner syndrome (WS), BLM gene in Bloom syndrome (BS), and RECQ4 in Rhothmund-Thomson's syndrome. These syndromes are characterized by premature ageing, graying and loss of hair, cancer, type II diabetes, osteoporosis, and atherosclerosis, all of which are diseases that are common at old age. These diseases are associated with high incidence of chromosomal abnormalities, including chromosome breaks, complex rearrangements, deletions and translocations, site specific mutations, and in particular sister chromatid exchanges (more common in BS) that are believed to be caused by a high level of somatic recombination. The proper function of RecQ helicases requires the specific interaction with topoisomerase III (Top 3). Top 3 changes the topological status of DNA by binding and cleaving single stranded DNA and passing either a single stranded or a double stranded DNA segment through the transient break and finally religating the break. The interaction of RecQ helicase with topoisomerase III at the N-terminal region is involved in the suppression of spontaneous and damage induced recombination and the absence of this interaction results in a lethal or very severe phenotype. The emerging picture clearly is that RecQ helicases in concert with Top 3 are involved in maintaining genomic stability and integrity by controlling recombination events, and repairing DNA damage in the G2-phase of the cell cycle. The importance of RecQ for genomic integrity is exemplified by the diseases that arise as a consequence of mutations or malfunctions in RecQ helicases; thus it is crucial that RecQ is present and functional to ensure proper human growth and development.

Further reading

*Bernstein, Douglas A. and Keck, James L. (2003) Domain mapping of Escherichia coli RecQ defines the roles of conserved N- and C-terminal regions in the RecQ family. Nucleic Acids Research. 31; 2778- 2785.
*Cobb, Jennifer A. et al. (2002) RecQ helicases: at the heart of genetic stability. FEBS Letters. 529; 43-48.
*Skouboe, Camilla et al. (2005) Genome instability as a cause of ageing and cancer: Implications of RecQ helicases. Signal Transduction. 3: 142- 151.
*Laursen, Louise V. et al. (2003) RecQ helicases and topoisomerase III in cancer & aging. Biogerontology. 4: 275–287.

External links

* [http://sekelsky.bio.unc.edu/Research/RecQ.html RecQ Helicases] , introduction at UNC's Selsky Lab.
* [http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2003/Baxter/BLMgene.html BLM gene encodes a RecQ Helicase] , description of the gene