RecQ helicase is a family ofhelicaseenzymes initially found inEscherichia coli^[1] that has been shown to be important in genome maintenance.^[2][3][4] They function through catalyzing the reactionATP + 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 reactionNTP + H₂O → NDP + P to drive the unwinding of eitherDNA orRNA.

In prokaryotes RecQ is necessary for plasmidrecombination 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.^{[citation needed]}

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.^{[citation needed]}

There are at least five human RecQ genes; and mutations in three human RecQ genes are implicated in heritable human diseases:WRN gene inWerner syndrome (WS),BLM gene inBloom syndrome (BS), andRECQL4 inRothmund–Thomson syndrome.^[5] These syndromes are characterized by premature aging, and can give rise to the diseases ofcancer, type 2diabetes,osteoporosis, andatherosclerosis, 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 specificmutations, and in particular sister chromatid exchanges (more common in BS) that are believed to be caused by a high level of somatic recombination.^{[citation needed]}

The proper function of RecQ helicases requires the specific interaction withtopoisomerase 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 re-ligating 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.^{[citation needed]}

TheWerner syndrome ATP-dependenthelicase (WRN helicase) is unusual among RecQ DNA family helicases in having an additionalexonuclease activity. WRN interacts withDNA-PKcs and theKu protein complex. This observation, combined with evidence that WRN deficient cells produce extensive deletions at sites of joining of non-homologous DNA ends, suggests a role for WRN protein in the DNA repair process ofnon-homologous end joining (NHEJ).^[6] WRN also physically interacts with the major NHEJ factor X4L4 (XRCC4-DNA ligase 4 complex).^[7] X4L4 stimulates WRN exonuclease activity that likely facilitates DNA end processing prior to final ligation by X4L4.^[7]

WRN also appears to play a role in resolving recombination intermediate structures duringhomologous recombinational repair (HRR) of DNA double-strand breaks.^[6]

WRN participates in a complex withRAD51, RAD54,RAD54B andATR proteins in carrying out the recombination step during inter-strandDNA cross-link repair.^[8]

Evidence was presented that WRN plays a direct role in the repair ofmethylation inducedDNA damage. The process likely involves thehelicase andexonuclease activities of WRN that operate together withDNA polymerase beta in long patchbase excision repair.^[9]

WRN was found to have a specific role in preventing or repairing DNA damages resulting from chronicoxidative stress, particularly in slowly replicating cells.^[10] This finding suggested that WRN may be important in dealing with oxidative DNA damages that underlie normal aging^[10] (seeDNA damage theory of aging).

Cells from humans withBloom syndrome are sensitive to DNA damaging agents such asUV andmethyl methanesulfonate^[11] indicating deficientDNA repair capability.

The budding yeastSaccharomyces cerevisiae encodes an ortholog of the Bloom syndrome (BLM) protein that is designatedSgs1 (Small growth suppressor 1). Sgs1(BLM) is a helicase that functions inhomologous recombinational repair of DNA double-strand breaks. The Sgs1(BLM) helicase appears to be a central regulator of most of the recombination events that occur duringS. cerevisiaemeiosis.^[12] During normal meiosis Sgs1(BLM) is responsible for directing recombination towards the alternate formation of either early non-crossovers orHolliday junction joint molecules, the latter being subsequently resolved ascrossovers.^[12]

In the plantArabidopsis thaliana, homologs of the Sgs1(BLM) helicase act as major barriers to meiotic crossover formation.^[13] These helicases are thought to displace the invading strand allowing its annealing with the other 3'overhang end of the double-strand break, leading to non-crossover recombinant formation by a process calledsynthesis-dependent strand annealing (SDSA) (see Wikipedia article "Genetic recombination"). It is estimated that only about 5% of double-strand breaks are repaired by crossover recombination. Sequela-Arnaud et al.^[13] suggested that crossover numbers are restricted because of the long-term costs of crossover recombination, that is, the breaking up of favorable genetic combinations of alleles built up by pastnatural selection.

In humans, individuals withRothmund–Thomson syndrome, and carrying theRECQL4 germlinemutation, have several clinical features of acceleratedaging. These features include atrophic skin and pigment changes,alopecia,osteopenia,cataracts and an increased incidence ofcancer.^[14] RECQL4 mutant mice also show features of accelerated aging.^[15]

RECQL4 has a crucial role inDNA end resection that is the initial step required forhomologous recombination (HR)-dependent double-strand break repair.^[16] When RECQL4 is depleted, HR-mediated repair and 5' end resection are severely reducedin vivo. RECQL4 also appears to be necessary for other forms ofDNA repair includingnon-homologous end joining,nucleotide excision repair andbase excision repair.^[14] The association of deficient RECQL4 mediated DNA repair with accelerated aging is consistent with theDNA damage theory of aging.

• Bloom syndrome

• RecQ HelicasesArchived 2004-11-02 at theWayback Machine, introduction atUNC's Sekelsky Lab.
• BLM gene encodes a RecQ Helicase, description of the gene

• Genes on human chromosome 15
• Genes on human chromosome 8
• Genes on human chromosome 17
• Genes on human chromosome 9
• EC 3.6.1
• Aging-related enzymes
• Helicases
• Senescence
• DNA repair

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