(DNA巻き戻し修復酵素)RecQヘリカーゼ

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rheniumの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/19 15:21:07」(JST)

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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^[1] that has been shown to be important in genome maintenance.^[2]^[3]^[4] 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.^[5] 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.

References

^ Bernstein DA, Keck JL (June 2003). "Domain mapping of Escherichia coli RecQ defines the roles of conserved N- and C-terminal regions in the RecQ family". Nucleic Acids Res. 31 (11): 2778–85. doi:10.1093/nar/gkg376. PMC 156711. PMID 12771204.
^ Cobb JA, Bjergbaek L, Gasser SM (October 2002). "RecQ helicases: at the heart of genetic stability". FEBS Lett. 529 (1): 43–8. doi:10.1016/S0014-5793(02)03269-6. PMID 12354611.
^ Kaneko H, Fukao T, Kondo N (2004). "The function of RecQ helicase gene family (especially BLM) in DNA recombination and joining". Adv. Biophys. 38: 45–64. doi:10.1016/S0065-227X(04)80061-3. PMID 15493327.
^ Ouyang KJ, Woo LL, Ellis NA (2008). "Homologous recombination and maintenance of genome integrity: cancer and aging through the prism of human RecQ helicases". Mech. Ageing Dev. 129 (7-8): 425–40. doi:10.1016/j.mad.2008.03.003. PMID 18430459.
^ Hanada K, Hickson ID (September 2007). "Molecular genetics of RecQ helicase disorders". Cell. Mol. Life Sci. 64 (17): 2306–22. doi:10.1007/s00018-007-7121-z. PMID 17571213.

External links

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

UpToDate Contents

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English Journal

RECQ1 interacts with FEN-1 and promotes binding of FEN-1 to telomeric chromatin.

Sami F, Lu X, Parvathaneni S, Roy R, Gary RK, Sharma S.
The Biochemical journal.Biochem J.2015 Mar 16. [Epub ahead of print]
RecQ helicases are a family of highly conserved proteins that maintain genomic stability through their important roles in replication restart mechanisms. Cellular phenotypes of RECQ1 deficiency are indicative of aberrant repair of stalled replication forks, but the molecular functions of RECQ1, the
PMID 25774876

Unwinding forward and sliding back: an intermittent unwinding mode of the BLM helicase.

Wang S1, Qin W2, Li JH1, Lu Y1, Lu KY2, Nong DG1, Dou SX1, Xu CH3, Xi XG4, Li M1.
Nucleic acids research.Nucleic Acids Res.2015 Mar 12. pii: gkv209. [Epub ahead of print]
There are lines of evidence that the Bloom syndrome helicase, BLM, catalyzes regression of stalled replication forks and disrupts displacement loops (D-loops) formed during homologous recombination (HR). Here we constructed a forked DNA with a 3' single-stranded gap and a 5' double-stranded handle t
PMID 25765643

Action-at-a-Distance Mutagenesis Induced by Oxidized Guanine in Werner Syndrome Protein-Reduced Human Cells.

Kamiya H1, Yamazaki D, Nakamura E, Makino T, Kobayashi M, Matsuoka I, Harashima H.
Chemical research in toxicology.Chem Res Toxicol.2015 Mar 2. [Epub ahead of print]
8-Oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) in DNA is one of the most important oxidatively damaged bases and causes G:C → T:A substitution mutations. The Werner syndrome protein (WRN) is a cancer-related RecQ DNA helicase and plays many roles in DNA replication and repair. To examine the rela
PMID 25730140