DNA repair and recombination protein RAD54-like 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 ''RAD54L''

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, and 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, a protein known to be involved in the homologous recombination and repair of DNA. This protein has been shown to play a role in homologous recombination related repair of DNA double-strand breaks. The binding of this protein to double-strand DNA induces a DNA topological change, which is thought to facilitate homologous DNA pairing, and stimulate DNA recombination. RAD54 is one of the key proteins necessary for

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 ...

and

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 ...

in many organisms. Without functional RAD54, tumor development is more likely. RAD54 was initially described in the budding yeast ''Saccharomyces cerevisiae'' as being a member of the evolutionarily conserved RAD52 epistasis group, which additionally includes RAD51, RAD52, RAD55, and RAD57 factors. This group is believed to be involved in DNA recombination events and repair mechanisms, especially those involving double-stranded DNA breaks during both

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...

and

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...

. Recently a human homologue of the yeast RAD54 was discovered and termed hRAD54.

Human gene

Human RAD54, or hRAD54, is linked to chromosome 1p32. It encodes a protein, composed of 747 amino acids, that is 52% identical to its yeast counterpart. These two proteins also share many functional similarities. The RAD54 encoded product is a member of the Swi2/Snf2 protein family, a member of the Swi2/Snf2 subfamily of

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...

s. These protein products have homology in seven conserved helicase motifs. Purified hRAD54 has been shown to specifically exhibit DNA-dependent ATPase and

supercoiling DNA supercoiling refers to the amount of twist in a particular DNA strand, which determines the amount of strain on it. A given strand may be "positively supercoiled" or "negatively supercoiled" (more or less tightly wound). The amount of a st ...

activities. hRAD54 transcripts are expressed primarily in the testis and thymus, with lower levels being found also in the small intestines, colon, breast, and prostate. Mutants of hRAD54 are extremely sensitive to x-rays, as well as

methyl methanesulfonate Methyl methanesulfonate (MMS), also known as methyl mesylate, is an alkylating agent and a carcinogen. It is also a suspected reproductive toxicant, and may also be a skin/sense organ toxicant. It is used in cancer treatment.D-loops formed. An alternative function of RAD54 may be to remove RAD51 proteins after joints formation and recombination initiation has occurred.

Inactivation and cancer susceptibility

Defects in RAD51 are known to be associated with tumor development. Normally, RAD51 interacts with both

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 h ...

and

BRCA2 ''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...

protein products to cause tumor suppression. This leads to the assumption that other members of the RAD52 epistasis group, including RAD54, are also important in tumor development and suppression because of their homologous relationship. RAD54’s involvement as a necessary recombinational protein is supported in the finding that there are mutations of RAD54 in a small percentage of studied breast and colon carcinomas, as well as several lymphomas.

Meiosis

The frequency of spontaneous

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

breaks during

was measured in the

spermatocyte Spermatocytes are a type of male gametocyte in animals. They derive from immature germ cells called spermatogonia. They are found in the testis, in a structure known as the seminiferous tubules. There are two types of spermatocytes, primary and s ...

s of both wild type mice and ''Rad54/Rad54B'' knockout mice. In the ''Rad54/Rad54B'' knockout mice, the spontaneous

chromosome aberration A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...

frequency detected at metaphase 1 of

was more than 10-fold higher than in the wild-type mice. This finding, and additional experimental findings, indicated that the RAD54/RAD54B proteins have a role in maintaining a stable

karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...

during male meiosis.

Human gene

Inactivation and cancer susceptibility

Meiosis

References

Further reading