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Wednesday 17 September 2003

RecQ helicases represent a highly conserved family that is required for the maintenance of genome integrity. The RecQ helicases are highly conserved in evolution and are required for maintaining genome stability in all organisms.



The RecQ family is named after the RecQ protein of Escherichia coli, which is a component of the so-called RecF pathway of genetic recombination. Mutations of genes in this pathway lead to deficiency in conjugational recombination and sensitivity to UV light when the major pathway for recombination, defined by the RecBCD helicase, is impaired.

However, in an otherwise wild-type background, recQ mutants show an elevated frequency of illegitimate recombination.
The RecQ family includes representatives in prokaryotes and unicellular eukaryotes, as well as in vertebrates.


- In humans, loss of RecQ helicase function is associated with predisposition to cancer and/or premature ageing. RecQ helicases have several roles during S phase of the cell cycle, ranging from facilitating the resumption of DNA synthesis at sites of replication fork breakdown to resolving structures during the process of homologous recombination.

- RecQ helicases are considered to be ’caretaker’ tumour suppressors that suppress neoplastic transformation through control of chromosomal stability. They seem to maintain genomic stability by functioning at the interface between DNA replication and DNA repair.

- Many other similar caretakers are functionally linked to the RecQ helicases, indicating a possible common molecular basis for tumorigenesis in several apparently distinct cancer predisposition disorders.

- Human RecQ helicases make multiple physical interactions with other nuclear proteins that are required for DNA metabolism. Many of these interactions have a functional effect on the activity of one or both partners.

- RecQ helicases are proposed to function at the interface between DNA replication and recombination to ’repair’ damaged replication forks.


- RecQ family members share a highly conserved domain comprising approximately 450 amino acids, which includes seven sequence motifs found in many classes of DNA and RNA helicases. Amongst these motifs is an ATP binding sequence (the so-called Walker A-box) and a Dex H-box, which is a characteristic of the RecQ family.

- Outside this domain, there is only limited sequence similarity amongst the family members. Where studied, RecQ family members have been shown to be DNA helicases that translocate in the 3’ 5’ direction. WRN is unique in also being a 3’ 5’ exonuclease dependent upon a functionally separable domain in the N-terminal region of the protein.

Pathology: DNA helicases deficiencies

Defects in any of three RecQ family members (BLM, WRN or RECQ4) give rise to cancer predisposition disorders. These are Bloom’s syndrome, Werner’s syndrome and Rothmund-Thomson syndrome. Bloom’s syndrome is uniquely associated with a predisposition to cancers of all types.

- RECQL1: no disorder associated
- RECQL2 (MIM.604611): mutations in the Werner syndrome (MIM.277700)
- RECQL3 (BLM) (MIM.604610) (15q26.1): mutations in the Bloom syndrome (MIM.210900)
- RECQL4 (MIM.603781) : mutations in the Rothmund-Thomson syndrome (MIM.268400) and RAPADILINO syndrome
- RECQL5 (MIM.603781): no disorder associated


- Khakhar RR, Cobb JA, Bjergbaek L, Hickson ID, Gasser SM. RecQ helicases: multiple roles in genome maintenance. Trends Cell Biol. 2003 Sep;13(9):493-501. PMID: 12946629

- Hickson ID. RecQ helicases: caretakers of the genome. Nat Rev Cancer. 2003 Mar;3(3):169-78. PMID: 12612652

- Nakayama H. RecQ family helicases: roles as tumor suppressor proteins. Oncogene. 2002 Dec 16;21(58):9008-21. PMID: 12483516

- Shen JC, Loeb LA. The Werner syndrome gene: the molecular basis of RecQ helicase-deficiency diseases. Trends Genet. 2000 May;16(5):213-20. PMID: 10782115