RecQ helicase

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Bloom syndrome
Identifiers
Symbol BLM
Entrez 641
HUGO 1058
OMIM 604610
RefSeq NM_000057
UniProt P54132
Other data
Locus Chr. 15 [1]
RecQ protein-like 4
Identifiers
Symbol RECQL4
Entrez 9401
HUGO 9949
OMIM 603780
RefSeq NM_004260
UniProt O94761
Other data
Locus Chr. 8 q24.3
RecQ protein-like 5
Identifiers
Symbol RECQL5
Entrez 9400
HUGO 9950
OMIM 603781
RefSeq NM_004259
UniProt O94762
Other data
Locus Chr. 17 q25
RMI1, RecQ mediated genome instability 1
Identifiers
Symbol RMI1
Alt. symbols C9orf76
Entrez 80010
HUGO 25764
OMIM 610404
RefSeq NM_024945
UniProt Q9H9A7
Other data
Locus Chr. 9 q22.1
Werner syndrome
Identifiers
Symbol WRN
Entrez 7486
HUGO 12791
OMIM 604611
RefSeq NM_000553
UniProt Q14191
Other data
Locus Chr. 8 p

RecQ helicase is a family of helicase enzymes initially found in Escherichia coli[1] that has been shown to be important in genome maintenance.[2][3][4] They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H2O → NDP + P to drive the unwinding of either DNA or RNA.

Function[edit]

In prokaryotes RecQ is necessary for plasmid recombination and DNA repair from UV-light, free radicals, and alkylating agents. This protein can also reverse damage from replication errors. In eukaryotes, replication does not proceed normally in the absence of RecQ proteins, which also function in aging, silencing, recombination and DNA repair.

Structure[edit]

RecQ family members share three regions of conserved protein sequence referred to as the:

  • N-terminal – Helicase
  • middle – RecQ-conserved (RecQ-Ct) and
  • C-terminal – 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.

Clinical significance[edit]

There are at least five human RecQ genes; and mutations in 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 Rothmund-Thomson syndrome.[5] These syndromes are characterized by premature aging, and can give rise to the diseases of cancer, type 2 diabetes, osteoporosis, and atherosclerosis, which are commonly found in 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.

Mechanism[edit]

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.

References[edit]

  1. ^ Bernstein DA, Keck JL (June 2003). "Domain mapping of Escherichia coli RecQ defines the roles of conserved N- and C-terminal regions in the RecQ family". Nucleic Acids Res. 31 (11): 2778–85. doi:10.1093/nar/gkg376. PMC 156711. PMID 12771204. 
  2. ^ Cobb JA, Bjergbaek L, Gasser SM (October 2002). "RecQ helicases: at the heart of genetic stability". FEBS Lett. 529 (1): 43–8. doi:10.1016/S0014-5793(02)03269-6. PMID 12354611. 
  3. ^ Kaneko H, Fukao T, Kondo N (2004). "The function of RecQ helicase gene family (especially BLM) in DNA recombination and joining". Adv. Biophys. 38: 45–64. doi:10.1016/S0065-227X(04)80061-3. PMID 15493327. 
  4. ^ Ouyang KJ, Woo LL, Ellis NA (2008). "Homologous recombination and maintenance of genome integrity: cancer and aging through the prism of human RecQ helicases". Mech. Ageing Dev. 129 (7-8): 425–40. doi:10.1016/j.mad.2008.03.003. PMID 18430459. 
  5. ^ Hanada K, Hickson ID (September 2007). "Molecular genetics of RecQ helicase disorders". Cell. Mol. Life Sci. 64 (17): 2306–22. doi:10.1007/s00018-007-7121-z. PMID 17571213. 

Further reading[edit]

  • Skouboe C, Bjergbaek L, Andersen AH (2005). "Genome instability as a cause of ageing and cancer: Implications of RecQ helicases". Signal Transduction 5 (3): 142–151. doi:10.1002/sita.200400052. 
  • Laursen LV, Bjergbaek L, Murray JM, Andersen AH (2003). "RecQ helicases and topoisomerase III in cancer and aging". Biogerontology 4 (5): 275–87. doi:10.1023/A:1026218513772. PMID 14618025. 

External links[edit]