RAD18: Difference between revisions

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{{Infobox_gene}}
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'''E3 ubiquitin-protein ligase RAD18''' is an [[enzyme]] that in humans is encoded by the ''RAD18'' [[gene]].<ref name="pmid10884424">{{cite journal |vauthors=Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M | title = Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens | journal = Proc Natl Acad Sci U S A | volume = 97 | issue = 14 | pages = 7927–32 |date=Aug 2000 | pmid = 10884424 | pmc = 16647 | doi =10.1073/pnas.97.14.7927 }}</ref><ref name="pmid10908344">{{cite journal |vauthors=Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z | title = The human RAD18 gene product interacts with HHR6A and HHR6B | journal = Nucleic Acids Res | volume = 28 | issue = 14 | pages = 2847–54 |date=Sep 2000 | pmid = 10908344 | pmc = 102657 | doi =10.1093/nar/28.14.2847 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56852| accessdate = }}</ref>
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{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = RAD18 homolog (S. cerevisiae)
| HGNCid = 18278
| Symbol = RAD18
| AltSymbols =; RNF73
| OMIM = 605256
| ECnumber =
| Homologene = 48572
| MGIid = 1890476
  | Function = {{GNF_GO|id=GO:0003684 |text = damaged DNA binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0000785 |text = chromatin}} {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006281 |text = DNA repair}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 56852
    | Hs_Ensembl = ENSG00000070950
    | Hs_RefseqProtein = NP_064550
    | Hs_RefseqmRNA = NM_020165
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 8893760
    | Hs_GenLoc_end = 8980186
    | Hs_Uniprot = Q9NS91
    | Mm_EntrezGene = 58186
    | Mm_Ensembl = ENSMUSG00000030254
    | Mm_RefseqmRNA = NM_021385
    | Mm_RefseqProtein = NP_067360
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 112585662
    | Mm_GenLoc_end = 112662447
    | Mm_Uniprot = Q8CED3
  }}
}}
'''RAD18 homolog (S. cerevisiae)''', also known as '''RAD18''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56852| accessdate = }}</ref>


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| section_title =  
| section_title =  
| summary_text = The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring-finger motif.  Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.<ref name="entrez">{{cite web | title = Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56852| accessdate = }}</ref>
| summary_text = The protein encoded by this gene is highly similar to [[S. cerevisiae]] DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring finger motif.  Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.<ref name="entrez"/>
}}
}}
==Animal models==
[[Model organism]]s have been used in the study of ''RAD18'' function. A [[conditional gene knockout|conditional]] [[knockout mouse]] line, called ''Rad18<sup>tm1a(EUCOMM)Wtsi</sup>'',<ref>{{cite web |url=http://www.knockoutmouse.org/martsearch/project/32691 |title=Rad18<sup>tm1a(EUCOMM)Wtsi</sup> |author=[[EUCOMM]] |work= |publisher={{URL|www.knockoutmouse.org}}}}</ref> was generated as part of the [[EUCOMM]] program — a high-throughput [[mutagenesis]] project to generate and distribute animal models of disease to interested scientists — at the [[Wellcome Trust Sanger Institute]].<ref name="pmid21677750">{{Cite journal
| last1 = Skarnes |first1 =W. C.
| doi = 10.1038/nature10163
| last2 = Rosen | first2 = B.
| last3 = West | first3 = A. P.
| last4 = Koutsourakis | first4 = M.
| last5 = Bushell | first5 = W.
| last6 = Iyer | first6 = V.
| last7 = Mujica | first7 = A. O.
| last8 = Thomas | first8 = M.
| last9 = Harrow | first9 = J.
| last10 = Cox | first10 = T.
| last11 = Jackson | first11 = D.
| last12 = Severin | first12 = J.
| last13 = Biggs | first13 = P.
| last14 = Fu | first14 = J.
| last15 = Nefedov | first15 = M.
| last16 = De Jong | first16 = P. J.
| last17 = Stewart | first17 = A. F.
| last18 = Bradley | first18 = A.
| title = A conditional knockout resource for the genome-wide study of mouse gene function
| journal = Nature
| volume = 474
| issue = 7351
| pages = 337–342
| year = 2011
| pmid = 21677750
| pmc =3572410
}}</ref><ref name="Vanderweyden">{{cite journal |author=Van der Weyden L, White JK, Adams, DA, Logan DW |title=The mouse genetics toolkit: revealing function and mechanism |journal=[[Genome Biology]]|volume=12 |issue=6 |page=224 |date=June 2011 |pmid=21722353|doi=10.1186/gb-2011-12-6-224  |url=http://genomebiology.com/2011/12/6/224 |pmc=3218837}}</ref><ref name="Dolgin">{{cite journal |author=Dolgin E |title=Mouse library set to be knockout |journal=Nature|volume=474 |issue= |pages=262–263 |date=June 2011 |pmid=21677718|doi=10.1038/474262a  |url=http://www.nature.com/news/2011/110615/full/474262a.html}}</ref><ref name="pmid17218247">{{cite journal |vauthors=Collins FS, Rossant J, Wurst W |title=A mouse for all reasons |journal=Cell |volume=128 |issue=1 |pages=9–13 |date=January 2007 |pmid=17218247 |doi=10.1016/j.cell.2006.12.018 |url=}}</ref><ref name="pmid15340424">{{cite journal  |vauthors=Auwerx J, Avner P, Baldock R, etal |title=The European dimension for the mouse genome mutagenesis program |journal=Nat. Genet. |volume=36 |issue=9 |pages=925–7 |date=September 2004 |pmid=15340424 |pmc=2716028 |doi=10.1038/ng0904-925 |url=}}</ref> Mice lacking ''Rad18'' had no significant defects in viability or [[fertility]],<ref>{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/viability-at-weaning/ |title=
Viability at Weaning Data for Rad18 |author=Wellcome Trust Sanger Institute |work=Mouse Resources Portal |publisher={{URL|www.sanger.ac.uk}}}}</ref><ref>{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/fertility/ |title=Fertility Data for Rad18 |author=Wellcome Trust Sanger Institute |work=Mouse Resources Portal |publisher={{URL|www.sanger.ac.uk}}}}</ref> therefore  male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="Vanderweyden"/><ref name="mgp_reference"/><ref name=screen>{{cite web |url=http://www.sanger.ac.uk/mouseportal/search?query=Rad18 |title=MGP Phenotyping of Rad18<sup>tm1a(EUCOMM)Wtsi</sup> |author=[[Wellcome Trust Sanger Institute]] |work=Mouse Resources Portal |publisher={{URL|www.sanger.ac.uk}}}}</ref>
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Rad18'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#C40000"|Abnormal<ref name="Body weight">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/weight-curves/ |title=Body weight data for Rad18 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal<ref name="Dysmorphology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/dysmorphology/ |title=Dysmorphology data for Rad18 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Indirect calorimetry]] || bgcolor="#C40000"|Abnormal<ref name="Indirect calorimetry">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/indirect-calorimetry/ |title=Indirect calorimetry data for Rad18 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#C40000"|Abnormal<ref name="DEXA">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/body-composition-dexa/ |title=DEXA data for Rad18 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#C40000"|Abnormal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Tail epidermis wholemount || bgcolor="#488ED3"|Normal
|-
| Skin Histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/salmonella-challenge/ |title=''Salmonella'' infection data for Rad18 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAIL/citrobacter-challenge/ |title=''Citrobacter'' infection data for Rad18 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | last1 = Gerdin | first1 = AK | journal = Acta Ophthalmologica | volume = 88 | pages =  925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
Twenty five tests were carried out and four significant [[phenotypes]] were reported:<ref name=screen/>
* [[Mutant]] male mice had a decreased [[body weight]] compared to [[wildtype]] control mice.
* Mutant male mice showed increased activity, [[VO2 max|VO2]] and [[energy expenditure]], determined by [[indirect calorimetry]].
* [[Dual-energy X-ray absorptiometry]] (DEXA) showed mutant male mice had a decrease in [[fat]] mass.
* A [[micronucleus test]] found a potential increase in [[DNA damage]] in mutant mice.
==Interactions==
RAD18 has been shown to [[Protein-protein interaction|interact]] with [[HLTF]],<ref name=pmid18316726>{{cite journal |last=Unk |first=Ildiko |authorlink= |author2=Hajdú Ildikó |author3=Fátyol Károly |author4=Hurwitz Jerard |author5=Yoon Jung-Hoon |author6=Prakash Louise |author7=Prakash Satya |author8=Haracska Lajos  |date=Mar 2008 |title=Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination |journal=[[PNAS|Proc. Natl. Acad. Sci. U.S.A.]] |volume=105 |issue=10 |pages=3768–73 |publisher= |location = United States| issn = | pmid = 18316726 |doi = 10.1073/pnas.0800563105 | bibcode = | url = |pmc=2268824 }}</ref> [[UBE2B]]<ref name=pmid10884424 /><ref name=pmid10908344 /> and [[UBE2A]].<ref name=pmid10884424/><ref name=pmid10908344/>


==References==
==References==
{{reflist|2}}
{{reflist|2}}
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin|35em}}
{{PBB_Further_reading  
{{PBB_Further_reading
| citations =  
| citations =  
*{{cite journal  | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
*{{cite journal  |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
*{{cite journal   |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3  }}
*{{cite journal  | author=Tateishi S, Sakuraba Y, Masuyama S, ''et al.'' |title=Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 14 |pages= 7927-32 |year= 2000 |pmid= 10884424 |doi=  }}
*{{cite journal  |vauthors=Mulder LC, Chakrabarti LA, Muesing MA |title=Interaction of HIV-1 integrase with DNA repair protein hRad18. |journal=J. Biol. Chem. |volume=277 |issue= 30 |pages= 27489–93 |year= 2002 |pmid= 12016221 |doi=10.1074/jbc.M203061200 }}
*{{cite journal | author=Xin H, Lin W, Sumanasekera W, ''et al.'' |title=The human RAD18 gene product interacts with HHR6A and HHR6B. |journal=Nucleic Acids Res. |volume=28 |issue= 14 |pages= 2847-54 |year= 2000 |pmid= 10908344 |doi= }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |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 }}
*{{cite journal | author=Mulder LC, Chakrabarti LA, Muesing MA |title=Interaction of HIV-1 integrase with DNA repair protein hRad18. |journal=J. Biol. Chem. |volume=277 |issue= 30 |pages= 27489-93 |year= 2002 |pmid= 12016221 |doi= 10.1074/jbc. M203061200 }}
*{{cite journal   |vauthors=Nikiforov AA, Sasina LK, Svetlova MP, etal |title=Early immobilization of nuclease FEN1 and accumulation of hRAD18 protein at stalled DNA replication forks in mammalian cells. |journal=Dokl. Biochem. Biophys. |volume=389 |issue= |pages= 122–5 |year= 2004 |pmid= 12856420 |doi=10.1023/A:1023696425171  }}
*{{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=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal | author=Nikiforov AA, Sasina LK, Svetlova MP, ''et al.'' |title=Early immobilization of nuclease FEN1 and accumulation of hRAD18 protein at stalled DNA replication forks in mammalian cells. |journal=Dokl. Biochem. Biophys. |volume=389 |issue= |pages= 122-5 |year= 2004 |pmid= 12856420 |doi=  }}
*{{cite journal   |vauthors=Beausoleil SA, Jedrychowski M, Schwartz D, etal |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal   |vauthors=Watanabe K, Tateishi S, Kawasuji M, etal |title=Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination. |journal=EMBO J. |volume=23 |issue= 19 |pages= 3886–96 |year= 2005 |pmid= 15359278 |doi= 10.1038/sj.emboj.7600383  | pmc=522788 }}
*{{cite journal | author=Beausoleil SA, Jedrychowski M, Schwartz D, ''et al.'' |title=Large-scale characterization of HeLa cell nuclear phosphoproteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130-5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 }}
*{{cite journal   |vauthors=Nikiforov A, Svetlova M, Solovjeva L, etal |title=DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation. |journal=Biochem. Biophys. Res. Commun. |volume=323 |issue= 3 |pages= 831–7 |year= 2004 |pmid= 15381075 |doi= 10.1016/j.bbrc.2004.08.165 }}
*{{cite journal | author=Watanabe K, Tateishi S, Kawasuji M, ''et al.'' |title=Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination. |journal=EMBO J. |volume=23 |issue= 19 |pages= 3886-96 |year= 2005 |pmid= 15359278 |doi= 10.1038/sj.emboj.7600383 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |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 }}
*{{cite journal | author=Nikiforov A, Svetlova M, Solovjeva L, ''et al.'' |title=DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation. |journal=Biochem. Biophys. Res. Commun. |volume=323 |issue= 3 |pages= 831-7 |year= 2004 |pmid= 15381075 |doi= 10.1016/j.bbrc.2004.08.165 }}
*{{cite journal   |vauthors=Miyase S, Tateishi S, Watanabe K, etal |title=Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination. |journal=J. Biol. Chem. |volume=280 |issue= 1 |pages= 515–24 |year= 2005 |pmid= 15509568 |doi=10.1074/jbc.M409219200  }}
*{{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=Masuyama S, Tateishi S, Yomogida K, etal |title=Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions. |journal=Genes Cells |volume=10 |issue= 8 |pages= 753–62 |year= 2005 |pmid= 16098139 |doi= 10.1111/j.1365-2443.2005.00874.x }}
*{{cite journal | author=Miyase S, Tateishi S, Watanabe K, ''et al.'' |title=Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination. |journal=J. Biol. Chem. |volume=280 |issue= 1 |pages= 515-24 |year= 2005 |pmid= 15509568 |doi= 10.1074/jbc. M409219200 }}
*{{cite journal   |vauthors=Nousiainen M, Silljé HH, Sauer G, etal |title=Phosphoproteome analysis of the human mitotic spindle. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue= 14 |pages= 5391–6 |year= 2006 |pmid= 16565220 |doi= 10.1073/pnas.0507066103  | pmc=1459365 }}
*{{cite journal | author=Masuyama S, Tateishi S, Yomogida K, ''et al.'' |title=Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions. |journal=Genes Cells |volume=10 |issue= 8 |pages= 753-62 |year= 2005 |pmid= 16098139 |doi= 10.1111/j.1365-2443.2005.00874.x }}
*{{cite journal   |vauthors=Bi X, Barkley LR, Slater DM, etal |title=Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest. |journal=Mol. Cell. Biol. |volume=26 |issue= 9 |pages= 3527–40 |year= 2006 |pmid= 16611994 |doi= 10.1128/MCB.26.9.3527-3540.2006  | pmc=1447421 }}
*{{cite journal | author=Nousiainen M, Silljé HH, Sauer G, ''et al.'' |title=Phosphoproteome analysis of the human mitotic spindle. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue= 14 |pages= 5391-6 |year= 2006 |pmid= 16565220 |doi= 10.1073/pnas.0507066103 }}
*{{cite journal   |vauthors=Lloyd AG, Tateishi S, Bieniasz PD, etal |title=Effect of DNA repair protein Rad18 on viral infection. |journal=PLoS Pathog. |volume=2 |issue= 5 |pages= e40 |year= 2006 |pmid= 16710452 |doi= 10.1371/journal.ppat.0020040 | pmc=1463017 }}
*{{cite journal | author=Bi X, Barkley LR, Slater DM, ''et al.'' |title=Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest. |journal=Mol. Cell. Biol. |volume=26 |issue= 9 |pages= 3527-40 |year= 2006 |pmid= 16611994 |doi= 10.1128/MCB.26.9.3527-3540.2006 }}
*{{cite journal   |vauthors=Yuasa MS, Masutani C, Hirano A, etal |title=A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest. |journal=Genes Cells |volume=11 |issue= 7 |pages= 731–44 |year= 2006 |pmid= 16824193 |doi= 10.1111/j.1365-2443.2006.00974.x }}
*{{cite journal  | author=Lloyd AG, Tateishi S, Bieniasz PD, ''et al.'' |title=Effect of DNA repair protein Rad18 on viral infection. |journal=PLoS Pathog. |volume=2 |issue= 5 |pages= e40 |year= 2006 |pmid= 16710452 |doi= 10.1371/journal.ppat.0020040 }}
*{{cite journal   |vauthors=Beausoleil SA, Villén J, Gerber SA, etal |title=A probability-based approach for high-throughput protein phosphorylation analysis and site localization. |journal=Nat. Biotechnol. |volume=24 |issue= 10 |pages= 1285–92 |year= 2006 |pmid= 16964243 |doi= 10.1038/nbt1240 }}
*{{cite journal | author=Yuasa MS, Masutani C, Hirano A, ''et al.'' |title=A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest. |journal=Genes Cells |volume=11 |issue= 7 |pages= 731-44 |year= 2006 |pmid= 16824193 |doi= 10.1111/j.1365-2443.2006.00974.x }}
*{{cite journal   |vauthors=Olsen JV, Blagoev B, Gnad F, etal |title=Global, ''in vivo'', and site-specific phosphorylation dynamics in signaling networks. |journal=Cell |volume=127 |issue= 3 |pages= 635–48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 }}
*{{cite journal | author=Beausoleil SA, Villén J, Gerber SA, ''et al.'' |title=A probability-based approach for high-throughput protein phosphorylation analysis and site localization. |journal=Nat. Biotechnol. |volume=24 |issue= 10 |pages= 1285-92 |year= 2006 |pmid= 16964243 |doi= 10.1038/nbt1240 }}
*{{cite journal | author=Olsen JV, Blagoev B, Gnad F, ''et al.'' |title=Global, ''in vivo'', and site-specific phosphorylation dynamics in signaling networks. |journal=Cell |volume=127 |issue= 3 |pages= 635-48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 }}
}}
}}
{{refend}}
{{refend}}


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[[Category:Genes mutated in mice]]
[[Category:DNA repair]]

Revision as of 08:49, 10 September 2017

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Identifiers
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Orthologs
SpeciesHumanMouse
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View/Edit Human

E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene.[1][2][3]

The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.[3]

Animal models

Model organisms have been used in the study of RAD18 function. A conditional knockout mouse line, called Rad18tm1a(EUCOMM)Wtsi,[4] was generated as part of the EUCOMM program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[5][6][7][8][9] Mice lacking Rad18 had no significant defects in viability or fertility,[10][11] therefore male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[6][12][13]

Twenty five tests were carried out and four significant phenotypes were reported:[13]

Interactions

RAD18 has been shown to interact with HLTF,[21] UBE2B[1][2] and UBE2A.[1][2]

References

  1. ↑ 1.0 1.1 1.2 Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M (Aug 2000). "Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens". Proc Natl Acad Sci U S A. 97 (14): 7927–32. doi:10.1073/pnas.97.14.7927. PMC 16647. PMID 10884424.
  2. ↑ 2.0 2.1 2.2 Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z (Sep 2000). "The human RAD18 gene product interacts with HHR6A and HHR6B". Nucleic Acids Res. 28 (14): 2847–54. doi:10.1093/nar/28.14.2847. PMC 102657. PMID 10908344.
  3. ↑ 3.0 3.1 "Entrez Gene: RAD18 RAD18 homolog (S. cerevisiae)".
  4. ↑ EUCOMM. "Rad18tm1a(EUCOMM)Wtsi". www.knockoutmouse.org. External link in |publisher= (help)
  5. ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  6. ↑ 6.0 6.1 Van der Weyden L, White JK, Adams, DA, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  7. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474: 262–263. doi:10.1038/474262a. PMID 21677718.
  8. ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  9. ↑ Auwerx J, Avner P, Baldock R, et al. (September 2004). "The European dimension for the mouse genome mutagenesis program". Nat. Genet. 36 (9): 925–7. doi:10.1038/ng0904-925. PMC 2716028. PMID 15340424.
  10. ↑ Wellcome Trust Sanger Institute. "Viability at Weaning Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
  11. ↑ Wellcome Trust Sanger Institute. "Fertility Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
  12. ↑ 12.0 12.1 Gerdin, AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  13. ↑ 13.0 13.1 Wellcome Trust Sanger Institute. "MGP Phenotyping of Rad18tm1a(EUCOMM)Wtsi". Mouse Resources Portal. www.sanger.ac.uk. External link in |publisher= (help)
  14. ↑ "Body weight data for Rad18". Wellcome Trust Sanger Institute.
  15. ↑ "Dysmorphology data for Rad18". Wellcome Trust Sanger Institute.
  16. ↑ "Indirect calorimetry data for Rad18". Wellcome Trust Sanger Institute.
  17. ↑ "DEXA data for Rad18". Wellcome Trust Sanger Institute.
  18. ↑ "Salmonella infection data for Rad18". Wellcome Trust Sanger Institute.
  19. ↑ "Citrobacter infection data for Rad18". Wellcome Trust Sanger Institute.
  20. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  21. ↑ Unk, Ildiko; Hajdú Ildikó; Fátyol Károly; Hurwitz Jerard; Yoon Jung-Hoon; Prakash Louise; Prakash Satya; Haracska Lajos (Mar 2008). "Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination". Proc. Natl. Acad. Sci. U.S.A. United States. 105 (10): 3768–73. doi:10.1073/pnas.0800563105. PMC 2268824. PMID 18316726.

Further reading

Retrieved from "https://www.wikidoc.org/index.php?title=RAD18&oldid=1413124"