DNA repair and recombination protein RAD54B is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''RAD54B''
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 ba ...
.
The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'' RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer.
Interactions
RAD54B has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
RAD51.
Cancer
The ''RAD54B''
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 ba ...
is somatically
mutated
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
or deleted in numerous types of cancer including
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
(~3.3%),
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
(~3.4%), and
lung cancer
Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
(~2.6%).
In North America, these three cancers alone account for about 20,500 individuals diagnosed annually with ''RAD54B'' defective cancer. In a pre-clinical study, colon cancer cells defective in ''RAD54B'' were determined to be selectively killed by inhibitors of the
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
protein
PARP1
Poly DP-ribosepolymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly DP-ribosesynthase 1 is an enzyme that in humans is encoded by the ''PARP1'' gene. It is the most abundant of the PARP family of enzymes, accounting for 90% o ...
.
Inhibitors of PARP1 likely impede alternative DNA repair responses that might otherwise compensate for loss of the ''RAD54B'' pathway in cancer cells. Thus ''RAD54B''-deficient cancer cells treated with a PARP1 inhibitor are apparently more vulnerable to killing by
naturally occurring DNA damages than non-cancerous cells without a RAD54 defect (see article
Synthetic lethality
Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death or death of an organism. Although the foregoing explanation is wider than this, it is common when referring to synthet ...
).
References
Further reading
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