DNA repair protein RAD50, also known as RAD50, 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 ''RAD50''
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 ...
.
Function
The protein encoded by this gene is highly similar to ''
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 ...
'' Rad50, a protein involved in
DNA double-strand break repair. This protein forms a complex with
MRE11
Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the ''MRE11'' gene. The gene has been designated ''MRE11A'' to distinguish it from the pseudogene ''MRE11B'' that is nowadays named ''MRE11P1''.
Function
This ge ...
and
NBS1
Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the ''NBN'' gene.
Function
Nibrin is a protein associated with the repair of double strand breaks (DSBs) which pose serious damage to a genome. It is a 754 amino ac ...
(also known as Xrs2 in yeast). This
MRN complex (MRX complex in yeast) binds to broken DNA ends and displays numerous enzymatic activities that are required for double-strand break repair by nonhomologous end-joining or homologous recombination.
Gene knockout studies of the mouse homolog of Rad50 suggest it is essential for cell growth and viability. Two alternatively spliced transcript variants of Rad50, which encode distinct proteins, have been reported.
Structure
Rad50 is a member of the
structural maintenance of chromosomes (SMC) family of proteins.
Like other SMC proteins, Rad50 contains a long internal
coiled-coil
A coiled coil is a structural motif in proteins in which 2–7
alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...
domain that folds back on itself, bringing the N- and C-termini together to form a globular
ABC ATPase head domain. Rad50 can dimerize both through its head domain and through a zinc-binding dimerization motif at the opposite end of the coiled-coil known as the “zinc-hook”.
Results from atomic force microscopy suggest that in free Mre11-Rad50-Nbs1 complexes, the zinc-hooks of a single Rad50 dimer associate to form a closed loop, while the zinc-hooks snap apart upon binding DNA, adopting a conformation that is thought to enable zinc-hook-mediated tethering of broken DNA ends.
Interactions
Rad50 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:
*
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a ...
,
* MRE11A
Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the ''MRE11'' gene. The gene has been designated ''MRE11A'' to distinguish it from the pseudogene ''MRE11B'' that is nowadays named ''MRE11P1''.
Function
This ge ...
,
* NBN,
* RINT1
RAD50-interacting protein 1 is a protein that in humans is encoded by the ''RINT1'' gene.
Interactions
RINT1 has been shown to interact with Rad50
DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the '' ...
,
* TERF2IP
Telomeric repeat-binding factor 2-interacting protein 1 also known as repressor activator protein 1 (Rap1) is a protein that in humans is encoded by the ''TERF2IP'' gene.
Interactions
TERF2IP has been shown to interact with Ku80, Rad50
DNA ...
, and
* TERF2
Telomeric repeat-binding factor 2 is a protein that is present at telomeres throughout the cell cycle. It is also known as TERF2, TRF2, and TRBF2, and is encoded in humans by the ''TERF2'' gene. It is a component of the shelterin nucleoprotein c ...
.
Evolutionary ancestry
Rad50 protein has been mainly studied in eukaryotes. However, recent work has shown that orthologs
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...
of the Rad50 protein are also conserved in extant prokaryotic
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
where they likely function in homologous recombinational repair. In the hyperthermophilic archeon ''Sulfolobus acidocaldarius
''Sulfolobus acidocaldarius'' is a thermoacidophilic archaeon that belongs to the phylum Thermoproteota. ''S. acidocaldarius'' was the first ''Sulfolobus'' species to be described, in 1972 by Thomas D. Brock and collaborators. This species was ...
'', the Rad50 and Mre11 proteins interact and appear to have an active role in repair of DNA damages introduced by gamma radiation. These findings suggest that eukaryotic Rad50 may be descended from an ancestral archaeal Rad50 protein that served a role in homologous recombinational repair of DNA damage.
Diseases
Human RAD50 deficiency is an autosomal recessive syndrome that has been reported in patients with microcephaly and short stature. Their clinical phenotype resembled Nijmegen Breakage Syndrome. Cells from these patients showed increased radiosensitity with an impaired response to chromosome breaks.
See also
* MRN complex
*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 ...
* Nijmegen Breakage Syndrome
References
Further reading
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External links
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* {{UCSC gene details, RAD50