ATP-dependent DNA helicase Q4 is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''RECQL4''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Mutations in ''RECQL4'' are associated with the autosomal recessive disease
Rothmund–Thomson syndrome
Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive skin condition.
There have been several reported cases associated with osteosarcoma. A hereditary basis, mutations in the DNA helicase ''RECQL4'' gene, causing problems during initi ...
, a disorder that has features of premature aging.
In addition to the Rothmund–Thomson syndrome, ''RECQL4'' mutations are also associated with
RAPADILINO and
Baller–Gerold syndrome
Baller–Gerold syndrome (BGS) is a rare genetic syndrome that involves premature fusion of the skull bones and malformations of facial, forearm and hand bones. The symptoms of Baller–Gerold syndrome overlap with features of a few other genetics ...
s.
There are two types of Rothmund Thomson syndrome and it is Type 2 that occurs in patients carrying deleterious mutations in both copies of the ''RECQL4'' gene. This condition is associated with a high risk of developing
osteosarcoma
An osteosarcoma (OS) or osteogenic sarcoma (OGS) (or simply bone cancer) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma ...
(malignant tumor of the bone).
''RECQL4'' gets its name from being homologous (sharing sequence) with other members of the
RecQ helicase
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 unwind ...
family. Two other genetic diseases are due to mutations in other RECQ helicases.
Bloom syndrome
Bloom syndrome (often abbreviated as BS in literature) is a rare autosomal recessive genetic disorder characterized by short stature, predisposition to the development of cancer, and genomic instability. BS is caused by mutations in the '' BLM'' ge ...
is associated with mutations in the ''BLM'' gene and
Werner syndrome
Werner syndrome (WS) or Werner's syndrome, also known as "adult progeria",James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . is a rare, autosomal recessive disorder ...
is associated with mutations in the ''WRN'' gene.
DNA repair
Double-strand breaks in DNA are potentially lethal to a cell and need to be repaired. Repair of double-strand breaks by
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
(HR) is an important cellular mechanism for avoiding this lethality. RECQL4 has a crucial role in the first step of HR, referred to as end resection.
When RECQL4 is deficient, end resection, and thus HR, is reduced. Evidence suggests that other forms of DNA repair including
non-homologous end joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direc ...
,
nucleotide excision repair
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucle ...
and
base excision repair
Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from ...
also depend on RECQL4 function.
In the Rothmund-Thomson syndrome, the association of deficient RECQL4-mediated DNA repair and premature aging is consistent with the
DNA damage theory of aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear D ...
.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Rothmund-Thomson Syndrome