Molecular genetics of RecQ helicase disorders

Abstract

The RecQ helicases belong to the Superfamily II group of DNA helicases, and are defined by amino acid motifs that show sequence similarity to the catalytic domain of Escherichia coli RecQ. RecQ helicases have crucial roles in the maintenance of genome stability. In humans, there are five RecQ helicases and deficiencies in three of them cause genetic disorders characterised by cancer predisposition, premature aging and/or developmental abnormalities. RecQ helicase-deficient cells exhibit aberrant genetic recombination and/or DNA replication, which result in chromosomal instability and a decreased potential for proliferation. Here, we review the current knowledge of the molecular genetics of RecQ helicases, focusing on the human RecQ helicase disorders and mouse models of these conditions.

DNA mismatch repair: Molecular mechanism, cancer, and ageing

“…members of the RecQ. helicase family, give rise to human segmental progeroid syndromes characterized by short telomeres and premature ageing or early onset of age-related disease such as cancer (reviewed in Blasco, 2007;Brosh and Bohr, 2007;Hanada and Hickson, 2007).…”

Determination of the biochemical properties of full-length human PIF1 ATPase

“…Thus, mutations in several DNA helicases of the RecQ family are associated with human diseases, such as Werner, Bloom and Rothmund-Thomson syndromes. [1][2][3] The PIF1 subfamily of 5' to 3' DNA helicases 4,5 is conserved from yeast to human. 6 In Saccharomyces cerevisiae (Sc), ScPif1 was first isolated due to its involvement in recombination and maintenance of mitochondrial DNA.…”

The mutation spectrum in RECQL4 diseases

“…33,34 In addition, defects in the BLM and WRN genes lead to severe inherited diseases (Bloom syndrome (MIM 210900) and Werner syndrome (MIM 277700)) having overlapping features with RECQL4 syndromes, such as cancer predisposition, growth retardation and developmental abnormalities. 35 The strongest expression of RECQL4 in human tissues was observed in the thymus and testis 32 whereas the most prominent expression was seen in developing bone, cartilage and intestine when studying expression in the mouse embryos (E15.5 and E18.5). 2 Three knockout mouse models were created for Recql4 to gain new information about the phenotype and the function of the gene and protein.…”