RecQ helicase is a family of helicase enzymes important in genome maintenance.
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.
RecQ protein is necessary for plasmid recombination and DNA repair from UV-light, free radicals, and alkylating agents, and 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 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.
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)
RECQL4 in Rothmund–Thomson syndrome.
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: breaks, complex rearrangements, deletions and translocations, site specific mutations, and in particular sister chromatid exchanges that are believed to be caused by a high level of somatic recombination.
The function of RecQ helicases requires the specific interaction with topoisomerase III (Top 3).
Topoisomerase III 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.
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.
Ot is crucial that RecQ is present and functional to ensure proper human growth and development
WRN plays a role in resolving recombination intermediate structures during homologous recombinational repair (HRR) of DNA double-strand breaks.
WRN plays a direct role in the repair of methylation induced DNA damage.
The process likely involves the helicase and exonuclease activities of WRN that operate together with DNA polymerase beta in long patch base excision repair.
WRN was found to have a specific role in preventing or repairing DNA damages resulting from chronic oxidative stress, particularly in slowly replicating cells.
WRN may be important in dealing with oxidative DNA damages that underlie normal aging.
Cells from humans with Bloom syndrome are sensitive to DNA damaging agents such as UV and methyl methanesulfonate indicating deficient DNA repair capability.
Sgs1(BLM) is a helicase that functions in homologous recombinational repair of DNA double-strand breaks, as a central regulator of most of the recombination events that occur during S. cerevisiae meiosis.
Individuals with Rothmund–Thomson syndrome, and carrying the RECQL4 germline mutation, have several clinical features of accelerated aging: atrophic skin and pigment changes, alopecia, osteopenia, cataracts and an increased incidence of cancer.
RECQL4 has a crucial role in DNA end resection that is the initial step required for homologous recombination (HR)-dependent double-strand break repair.
When RECQL4 is depleted, HR-mediated repair and 5’ end resection are severely reduced in vivo.
RECQL4 also appears to be necessary for other forms of DNA repair including non-homologous end joining, nucleotide excision repair and base excision repair.
The association of deficient RECQL4 mediated DNA repair with accelerated aging is consistent with the DNA damage theory of aging.