DNA repair and recombination protein RAD54-like

DNA repair and recombination protein RAD54-like
RAD54-like (S. cerevisiae)
Identifiers
Symbols RAD54L; HR54; RAD54A; hHR54; hRAD54
External IDs OMIM603615 MGI894697 HomoloGene48227 GeneCards: RAD54L Gene
RNA expression pattern
PBB GE RAD54L 204558 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8438 19366
Ensembl ENSG00000085999 ENSMUSG00000028702
UniProt Q92698 P70270
RefSeq (mRNA) NM_001142548.1 NM_009015
RefSeq (protein) NP_001136020.1 NP_033041
Location (UCSC) Chr 1:
46.71 – 46.74 Mb
Chr 4:
115.77 – 115.8 Mb
PubMed search [1] [2]

DNA repair and recombination protein RAD54-like is a protein that in humans is encoded by the RAD54L gene.[1][2]

The protein encoded by this gene belongs to the DEAD-like helicase superfamily, and shares similarity with Saccharomyces cerevisiae 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.[2]

Contents

Introduction to RAD54

RAD54 is one of the key proteins necessary for homologous recombination and DNA repair 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 and meiosis. Recently a human homologue of the yeast RAD54 was discovered and termed hRAD54.

Human RAD54 (hRAD54)

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 ATPases. These protein products have homology in seven conserved helicase motifs. Purified hRAD54 has been shown to specifically exhibit DNA-dependent ATPase and supercoiling 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 (MMS). These mutants are most likely defective in both the spontaneous and induced mitotic recombination processes.

Actions of hRAD54

The interaction between RAD54 and RAD51, another member of the RAD52 epistasis group, in humans is mediated by the N-terminal domain of the hRAD54 protein. This N-terminal end interacts with both the free and bound ends of the RAD51 protein. RAD54 moves along the length of the DNA, producing positive supercoils ahead of the replication protein movement and negative supercoils trailing the complex. The interaction with RAD51 enhances the ability of RAD54 to perform this supercoiling and strained opening activity. These proteins also work together to form DNA joints, with RAD54 specifically extending the joints and stabilizing the D-loops formed. An alternative function of RAD54 may be to remove RAD51 proteins after joints formation and recombination initiation has occurred.

Inactivation of hRAD54 and Cancer Susceptibility

Defects in RAD51 are known to be associated with tumor development. Normally, RAD51 interacts with both BRCA1 and BRCA2 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.

References

  1. ^ Kanaar R, Troelstra C, Swagemakers SM, Essers J, Smit B, Franssen JH, Pastink A, Bezzubova OY, Buerstedde JM, Clever B, Heyer WD, Hoeijmakers JH (Feb 1997). "Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: evidence for functional conservation". Curr Biol 6 (7): 828–38. doi:10.1016/S0960-9822(02)00606-1. PMID 8805304. 
  2. ^ a b "Entrez Gene: RAD54L RAD54-like (S. cerevisiae)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8438. 

Further reading



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  • RAD54B — RAD54 homolog B (S. cerevisiae), also known as RAD54B, is a human gene.cite web | title = Entrez Gene: RAD54B RAD54 homolog B (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=25788|… …   Wikipedia

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