RecQ helicase

Bloom syndrome
Identifiers
Symbol	BLM
Entrez	641
HUGO	1058
OMIM	604610
RefSeq	NM_000057
UniProt	P54132
Other data
Locus	Chr. 15 [1]

RecQ protein-like 4
Identifiers
Symbol	RECQL4
Entrez	9401
HUGO	9949
OMIM	603780
RefSeq	NM_004260
UniProt	O94761
Other data
Locus	Chr. 8 q24.3

RecQ protein-like 5
Identifiers
Symbol	RECQL5
Entrez	9400
HUGO	9950
OMIM	603781
RefSeq	NM_004259
UniProt	O94762
Other data
Locus	Chr. 17 q25

RMI1, RecQ mediated genome instability 1
Identifiers
Symbol	RMI1
Alt. symbols	C9orf76
Entrez	80010
HUGO	25764
OMIM	610404
RefSeq	NM_024945
UniProt	Q9H9A7
Other data
Locus	Chr. 9 q22.1

Werner syndrome
Identifiers
Symbol	WRN
Entrez	7486
HUGO	12791
OMIM	604611
RefSeq	NM_000553
UniProt	Q14191
Other data
Locus	Chr. 8 p

RecQ helicase is a family of helicase enzymes initially found in Escherichia coli that has been shown to be 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.

Function

In prokaryotes RecQ is necessary for plasmid recombination 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.

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.

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.

Clinical significance

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), and RECQ4 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, including chromosome breaks, complex rearrangements, deletions and translocations, site specific mutations, and in particular sister chromatid exchanges (more common in BS) that are believed to be caused by a high level of somatic recombination.

Mechanism

The proper function of RecQ helicases requires the specific interaction with topoisomerase 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 religating 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.

See also

• Bloom syndrome

External links

• RecQ Helicases, introduction at UNC's Sekelsky Lab.
• BLM gene encodes a RecQ Helicase, description of the gene