DNA repair and recombination protein RAD54-like: Difference between revisions

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{{Infobox_gene}}
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'''DNA repair and recombination protein RAD54-like''' is a [[protein]] that in humans is encoded by the ''RAD54L'' [[gene]].<ref name="pmid8805304">{{cite journal | vauthors = Kanaar R, Troelstra C, Swagemakers SM, Essers J, Smit B, Franssen JH, Pastink A, Bezzubova OY, Buerstedde JM, Clever B, Heyer WD, Hoeijmakers JH | title = Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: evidence for functional conservation | journal = Curr Biol | volume = 6 | issue = 7 | pages = 828–38 |date=Feb 1997 | pmid = 8805304 | pmc =  | doi =10.1016/S0960-9822(02)00606-1  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: RAD54L RAD54-like (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8438| accessdate = }}</ref>
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{{GNF_Protein_box
| image =
| image_source = 
| PDB =
| Name = RAD54-like (S. cerevisiae)
| HGNCid = 9826
| Symbol = RAD54L
| AltSymbols =; HR54; RAD54A; hHR54; hRAD54
| OMIM = 603615
| ECnumber = 
| Homologene = 48227
| MGIid = 894697
| GeneAtlas_image1 = PBB_GE_RAD54L_204558_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0004386 |text = helicase activity}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006310 |text = DNA recombination}} {{GNF_GO|id=GO:0007126 |text = meiosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 8438
    | Hs_Ensembl = ENSG00000085999
    | Hs_RefseqProtein = NP_003570
    | Hs_RefseqmRNA = NM_003579
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 46485991
    | Hs_GenLoc_end = 46516731
    | Hs_Uniprot = Q92698
    | Mm_EntrezGene = 19366
    | Mm_Ensembl = ENSMUSG00000028702
    | Mm_RefseqmRNA = NM_009015
    | Mm_RefseqProtein = NP_033041
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr = 4
    | Mm_GenLoc_start = 115594848
    | Mm_GenLoc_end = 115621617
    | Mm_Uniprot = P70270
  }}
}}
'''RAD54-like (S. cerevisiae)''', also known as '''RAD54L''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: RAD54L RAD54-like (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8438| accessdate = }}</ref>


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{{PBB_Summary
{{PBB_Summary
| section_title =  
| section_title =  
| summary_text = 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 paring, and stimulate DNA recombination.<ref name="entrez">{{cite web | title = Entrez Gene: RAD54L RAD54-like (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8438| accessdate = }}</ref>
| summary_text = 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.<ref name="entrez"/>
}}
}}


==  Introduction to RAD54 ==
==  Introduction to RAD54 ==
RAD54 is one of the key proteins necessary for [[Homologous recombination|homologous recombination]] and [[DNA repair|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|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|mitosis]] and [[Meiosis|meiosis]]. Recently a human homologue of the yeast RAD54 was discovered and termed hRAD54.  
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 (hRAD54) ==
Human RAD54, or hRAD54, is linked to chromosome 1p32. It encodes a protein, comprised 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]]. These protein products have homology in seven conserved helicase motifs. Purified hRAD54 has been shown to specifically exhibit DNA-dependent ATPase and [[DNA supercoil|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|methyl methanesulfonate]] (MMS). These mutants are most likely defective in both the spontaneous and induced mitotic recombination processes.
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]]s. These protein products have homology in seven conserved helicase motifs. Purified hRAD54 has been shown to specifically exhibit DNA-dependent ATPase and [[DNA supercoil|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 ==
== 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-loop|D-loops]] formed. An alternative function of RAD54 may be to remove RAD51 proteins after joints formation and recombination initiation has occurred.  
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-loop]]s 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 ==
== Inactivation of hRAD54 and Cancer Susceptibility ==
Defects in RAD51 are known to be associated with tumor development. Normally, RAD51 interacts with both [[BRCA1|BRCA1]] and [[BRCA2|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.
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==
==References==
{{reflist|2}}
{{reflist}}
*{{cite journal  | author=Golub EI, Kovalenko OV, Gupta RC, ''et al.'' |title=Interaction of human recombination proteins Rad51 and Rad54. |journal=Nucleic Acids Res. |volume=25 |issue= 20 |pages= 4106-10 |year= 1997 |pmid= 9321665 |doi=  }}
*{{cite journal  | vauthors=Golub EI, Kovalenko OV, Gupta RC |title=Interaction of human recombination proteins Rad51 and Rad54. |journal=Nucleic Acids Res. |volume=25 |issue= 20 |pages= 4106–10 |year= 1997 |pmid= 9321665 |doi=10.1093/nar/25.20.4106  | pmc=147015 |display-authors=etal}}
*{{cite journal  | author=Leone PE, Mendiola M, Alonso J, ''et al.'' |title=Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker. |journal=BMC Cancer |volume=3 |issue=  |pages= 6 |year= 2003 |pmid= 12614485 |doi=  }}
*{{cite journal  | vauthors=Leone PE, Mendiola M, Alonso J |title=Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker. |journal=BMC Cancer |volume=3|pages= 6 |year= 2003 |pmid= 12614485 |doi=10.1186/1471-2407-3-6 | pmc=152652  |display-authors=etal}}
*{{cite journal  | author=Rasio D, Murakumo Y, Robbins D, ''et al.'' |title=Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. |journal=Cancer Res. |volume=57 |issue= 12 |pages= 2378-83 |year= 1997 |pmid= 9192813 |doi=  }}
*{{cite journal  | vauthors=Rasio D, Murakumo Y, Robbins D |title=Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. |journal=Cancer Res. |volume=57 |issue= 12 |pages= 2378–83 |year= 1997 |pmid= 9192813 |doi=  |display-authors=etal}}
*{{cite journal  | author=Sigurdsson S, Van Komen S, Petukhova G, Sung P |title=Homologous DNA pairing by human recombination factors Rad51 and Rad54. |journal=J. Biol. Chem. |volume=277 |issue= 45 |pages= 42790-4 |year= 2003 |pmid= 12205100 |doi= 10.1074/jbc.M208004200 }}
*{{cite journal  | vauthors=Sigurdsson S, Van Komen S, Petukhova G, Sung P |title=Homologous DNA pairing by human recombination factors Rad51 and Rad54. |journal=J. Biol. Chem. |volume=277 |issue= 45 |pages= 42790–4 |year= 2003 |pmid= 12205100 |doi= 10.1074/jbc.M208004200 }}
*{{cite journal  | author=Swagemakers SM, Essers J, de Wit J, ''et al.'' |title=The human RAD54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase. |journal=J. Biol. Chem. |volume=273 |issue= 43 |pages= 28292-7 |year= 1998 |pmid= 9774452 |doi=  }}
*{{cite journal  | vauthors=Swagemakers SM, Essers J, de Wit J |title=The human RAD54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase. |journal=J. Biol. Chem. |volume=273 |issue= 43 |pages= 28292–7 |year= 1998 |pmid= 9774452 |doi=10.1074/jbc.273.43.28292 |display-authors=etal}}
 


==Further reading==
==Further reading==
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| citations =  
| citations =  
*{{cite journal  | author=Kanaar R, Troelstra C, Swagemakers SM, ''et al.'' |title=Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: evidence for functional conservation. |journal=Curr. Biol. |volume=6 |issue= 7 |pages= 828-38 |year= 1997 |pmid= 8805304 |doi=  }}
*{{cite journal  | vauthors=Rasio D, Murakumo Y, Robbins D |title=Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. |journal=Cancer Res. |volume=57 |issue= 12 |pages= 2378–83 |year= 1997 |pmid= 9192813 |doi=  |display-authors=etal}}
*{{cite journal  | author=Rasio D, Murakumo Y, Robbins D, ''et al.'' |title=Characterization of the human homologue of RAD54: a gene located on chromosome 1p32 at a region of high loss of heterozygosity in breast tumors. |journal=Cancer Res. |volume=57 |issue= 12 |pages= 2378-83 |year= 1997 |pmid= 9192813 |doi=  }}
*{{cite journal  | vauthors=Golub EI, Kovalenko OV, Gupta RC |title=Interaction of human recombination proteins Rad51 and Rad54. |journal=Nucleic Acids Res. |volume=25 |issue= 20 |pages= 4106–10 |year= 1997 |pmid= 9321665 |doi=10.1093/nar/25.20.4106  | pmc=147015 |display-authors=etal}}
*{{cite journal  | author=Golub EI, Kovalenko OV, Gupta RC, ''et al.'' |title=Interaction of human recombination proteins Rad51 and Rad54. |journal=Nucleic Acids Res. |volume=25 |issue= 20 |pages= 4106-10 |year= 1997 |pmid= 9321665 |doi=  }}
*{{cite journal  | vauthors=Swagemakers SM, Essers J, de Wit J |title=The human RAD54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase. |journal=J. Biol. Chem. |volume=273 |issue= 43 |pages= 28292–7 |year= 1998 |pmid= 9774452 |doi=10.1074/jbc.273.43.28292 |display-authors=etal}}
*{{cite journal  | author=Swagemakers SM, Essers J, de Wit J, ''et al.'' |title=The human RAD54 recombinational DNA repair protein is a double-stranded DNA-dependent ATPase. |journal=J. Biol. Chem. |volume=273 |issue= 43 |pages= 28292-7 |year= 1998 |pmid= 9774452 |doi= }}
*{{cite journal  | vauthors=Matsuda M, Miyagawa K, Takahashi M |title=Mutations in the RAD54 recombination gene in primary cancers. |journal=Oncogene |volume=18 |issue= 22 |pages= 3427–30 |year= 1999 |pmid= 10362365 |doi= 10.1038/sj.onc.1202692 |display-authors=etal}}
*{{cite journal  | author=Matsuda M, Miyagawa K, Takahashi M, ''et al.'' |title=Mutations in the RAD54 recombination gene in primary cancers. |journal=Oncogene |volume=18 |issue= 22 |pages= 3427-30 |year= 1999 |pmid= 10362365 |doi= 10.1038/sj.onc.1202692 }}
*{{cite journal  | vauthors=Carling T, Imanishi Y, Gaz RD, Arnold A |title=Analysis of the RAD54 gene on chromosome 1p as a potential tumor-suppressor gene in parathyroid adenomas. |journal=Int. J. Cancer |volume=83 |issue= 1 |pages= 80–2 |year= 1999 |pmid= 10449612 |doi=10.1002/(SICI)1097-0215(19990924)83:1<80::AID-IJC15>3.0.CO;2-E  }}
*{{cite journal  | author=Carling T, Imanishi Y, Gaz RD, Arnold A |title=Analysis of the RAD54 gene on chromosome 1p as a potential tumor-suppressor gene in parathyroid adenomas. |journal=Int. J. Cancer |volume=83 |issue= 1 |pages= 80-2 |year= 1999 |pmid= 10449612 |doi=  }}
*{{cite journal  | vauthors=Bello MJ, de Campos JM, Vaquero J |title=hRAD54 gene and 1p high-resolution deletion-mapping analyses in oligodendrogliomas. |journal=Cancer Genet. Cytogenet. |volume=116 |issue= 2 |pages= 142–7 |year= 2000 |pmid= 10640146 |doi=10.1016/S0165-4608(99)00122-3 |display-authors=etal}}
*{{cite journal  | author=Bello MJ, de Campos JM, Vaquero J, ''et al.'' |title=hRAD54 gene and 1p high-resolution deletion-mapping analyses in oligodendrogliomas. |journal=Cancer Genet. Cytogenet. |volume=116 |issue= 2 |pages= 142-7 |year= 2000 |pmid= 10640146 |doi=  }}
*{{cite journal  | vauthors=Pluth JM, Fried LM, Kirchgessner CU |title=Severe combined immunodeficient cells expressing mutant hRAD54 exhibit a marked DNA double-strand break repair and error-prone chromosome repair defect. |journal=Cancer Res. |volume=61 |issue= 6 |pages= 2649–55 |year= 2001 |pmid= 11289143 |doi=  }}
*{{cite journal  | author=Pluth JM, Fried LM, Kirchgessner CU |title=Severe combined immunodeficient cells expressing mutant hRAD54 exhibit a marked DNA double-strand break repair and error-prone chromosome repair defect. |journal=Cancer Res. |volume=61 |issue= 6 |pages= 2649-55 |year= 2001 |pmid= 11289143 |doi= }}
*{{cite journal  | vauthors=Ristic D, Wyman C, Paulusma C, Kanaar R |title=The architecture of the human Rad54-DNA complex provides evidence for protein translocation along DNA. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 15 |pages= 8454–60 |year= 2001 |pmid= 11459989 |doi= 10.1073/pnas.151056798  | pmc=37457 }}
*{{cite journal  | author=Ristic D, Wyman C, Paulusma C, Kanaar R |title=The architecture of the human Rad54-DNA complex provides evidence for protein translocation along DNA. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 15 |pages= 8454-60 |year= 2001 |pmid= 11459989 |doi= 10.1073/pnas.151056798 }}
*{{cite journal  | vauthors=Ren B, Cam H, Takahashi Y |title=E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. |journal=Genes Dev. |volume=16 |issue= 2 |pages= 245–56 |year= 2002 |pmid= 11799067 |doi= 10.1101/gad.949802  | pmc=155321 |display-authors=etal}}
*{{cite journal  | author=Ren B, Cam H, Takahashi Y, ''et al.'' |title=E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. |journal=Genes Dev. |volume=16 |issue= 2 |pages= 245-56 |year= 2002 |pmid= 11799067 |doi= 10.1101/gad.949802 }}
*{{cite journal  | vauthors=Sigurdsson S, Van Komen S, Petukhova G, Sung P |title=Homologous DNA pairing by human recombination factors Rad51 and Rad54. |journal=J. Biol. Chem. |volume=277 |issue= 45 |pages= 42790–4 |year= 2003 |pmid= 12205100 |doi= 10.1074/jbc.M208004200 }}
*{{cite journal  | author=Sigurdsson S, Van Komen S, Petukhova G, Sung P |title=Homologous DNA pairing by human recombination factors Rad51 and Rad54. |journal=J. Biol. Chem. |volume=277 |issue= 45 |pages= 42790-4 |year= 2003 |pmid= 12205100 |doi= 10.1074/jbc.M208004200 }}
*{{cite journal  | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 |display-authors=etal}}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | vauthors=Leone PE, Mendiola M, Alonso J |title=Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker. |journal=BMC Cancer |volume=3|pages= 6 |year= 2003 |pmid= 12614485 |doi=10.1186/1471-2407-3-6  | pmc=152652  |display-authors=etal}}
*{{cite journal  | author=Leone PE, Mendiola M, Alonso J, ''et al.'' |title=Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker. |journal=BMC Cancer |volume=3 |issue= |pages= 6 |year= 2003 |pmid= 12614485 |doi=  }}
*{{cite journal  | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | vauthors=Kim J, Bhinge AA, Morgan XC, Iyer VR |title=Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment. |journal=Nat. Methods |volume=2 |issue= 1 |pages= 47–53 |year= 2005 |pmid= 15782160 |doi= 10.1038/nmeth726 }}
*{{cite journal  | author=Kim J, Bhinge AA, Morgan XC, Iyer VR |title=Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment. |journal=Nat. Methods |volume=2 |issue= 1 |pages= 47-53 |year= 2005 |pmid= 15782160 |doi= 10.1038/nmeth726 }}
*{{cite journal  | vauthors=Thomä NH, Czyzewski BK, Alexeev AA |title=Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. |journal=Nat. Struct. Mol. Biol. |volume=12 |issue= 4 |pages= 350–6 |year= 2005 |pmid= 15806108 |doi= 10.1038/nsmb919 |display-authors=etal}}
*{{cite journal  | author=Thomä NH, Czyzewski BK, Alexeev AA, ''et al.'' |title=Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. |journal=Nat. Struct. Mol. Biol. |volume=12 |issue= 4 |pages= 350-6 |year= 2005 |pmid= 15806108 |doi= 10.1038/nsmb919 }}
*{{cite journal  | vauthors=Al-Wahiby S, Wong HP, Slijepcevic P |title=Shortened telomeres in murine scid cells expressing mutant hRAD54 coincide with reduction in recombination at telomeres. |journal=Mutat. Res. |volume=578 |issue= 1-2 |pages= 134–42 |year= 2005 |pmid= 15975611 |doi= 10.1016/j.mrfmmm.2005.04.008 }}
*{{cite journal  | author=Al-Wahiby S, Wong HP, Slijepcevic P |title=Shortened telomeres in murine scid cells expressing mutant hRAD54 coincide with reduction in recombination at telomeres. |journal=Mutat. Res. |volume=578 |issue= 1-2 |pages= 134-42 |year= 2005 |pmid= 15975611 |doi= 10.1016/j.mrfmmm.2005.04.008 }}
*{{cite journal  | vauthors=Gregory SG, Barlow KF, McLay KE |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315–21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 |display-authors=etal}}
*{{cite journal  | author=Gregory SG, Barlow KF, McLay KE, ''et al.'' |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315-21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
*{{cite journal  | vauthors=Bugreev DV, Mazina OM, Mazin AV |title=Rad54 protein promotes branch migration of Holliday junctions. |journal=Nature |volume=442 |issue= 7102 |pages= 590–3 |year= 2006 |pmid= 16862129 |doi= 10.1038/nature04889 }}
*{{cite journal  | author=Bugreev DV, Mazina OM, Mazin AV |title=Rad54 protein promotes branch migration of Holliday junctions. |journal=Nature |volume=442 |issue= 7102 |pages= 590-3 |year= 2006 |pmid= 16862129 |doi= 10.1038/nature04889 }}
*{{cite journal  | vauthors=Akiyama K, Yusa K, Hashimoto H |title=Rad54 is dispensable for the ALT pathway. |journal=Genes Cells |volume=11 |issue= 11 |pages= 1305–15 |year= 2007 |pmid= 17054727 |doi= 10.1111/j.1365-2443.2006.01020.x |display-authors=etal}}
*{{cite journal  | author=Akiyama K, Yusa K, Hashimoto H, ''et al.'' |title=Rad54 is dispensable for the ALT pathway. |journal=Genes Cells |volume=11 |issue= 11 |pages= 1305-15 |year= 2007 |pmid= 17054727 |doi= 10.1111/j.1365-2443.2006.01020.x }}
}}
}}
{{refend}}
{{refend}}
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Latest revision as of 18:35, 30 August 2017

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RefSeq (protein)

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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]

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. ↑ 2.0 2.1 "Entrez Gene: RAD54L RAD54-like (S. cerevisiae)".

Further reading


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