Helicases are molecular motor proteins that couple the hydrolysis of NTP to nucleic acid unwinding. The growing number of DNA helicases implicated in human disease suggests that their vital specialized roles in cellular pathways are important for the maintenance of genome stability. In particular, mutations in genes of the RecQ family of DNA helicases result in chromosomal instability diseases of premature aging and/or cancer predisposition. We will discuss the mechanisms of RecQ helicases in pathways of DNA metabolism. A review of RecQ helicases from bacteria to human reveals their importance in genomic stability by their participation with other proteins to resolve DNA replication and recombination intermediates. In the light of their known catalytic activities and protein interactions, proposed models for RecQ function will be summarized with an emphasis on how this distinct class of enzymes functions in chromosomal stability maintenance and prevention of human disease and cancer.
- DNA repair
- genomic instability
Abbreviations: ALT, alternative lengthening of telomeres; at, Arabidopsis thaliana; ATP[S], adenosine 5′-[γ-thio]triphosphate; BACH1, BRCA1-associated C-terminal helicase; BaP, benzo[a]pyrene; BcPh, benzo[c]phenanthrene; BER, base excision repair; BLAP75, BLM-associated protein 75; BS, Bloom syndrome; DE, diol epoxide; dm, Drosophila melanogaster; DNA-PK, DNA-dependent protein kinase; ds, double-stranded; DSB, double-strand break; ES, cells, embryonic stem cells; EXO-1, exonuclease 1; FEN-1, flap endonuclease 1; G4, G-quadruplex; HJ, Holliday junction; HR, homologous recombination; HRDC, helicase and RNaseD C-terminal; NHEJ, non-homologous end-joining; PARP-1, poly(ADP-ribose) polymerase-1; PCNA, proliferating cell nuclear antigen; PML, promyelocytic leukaemia; pol, DNA polymerase; RAPADILINO, syndrome, radial hypoplasia/aplasia, patellae hypoplasia/aplasia and cleft or highly arched palate, diarrhoea and dislocated joints, little size and limb malformation, nose slender and normal intelligence; rDNA, ribosomal DNA; RPA, replication protein A; RQC, RecQ C-terminal; RTS, Rothmund–Thomson syndrome; SCE, sister chromatid exchange; SDSA, synthesis-dependent strand annealing; SF, superfamily; ss, single-stranded; SSB, ssDNA-binding protein; t-loop, telomeric loop; Top3, topoisomerase III; TRF, telomeric repeat-binding factor; WEX, Werner-like exonuclease; WS, Werner syndrome
- The Biochemical Society, London