RAD18: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''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>
'''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 = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 14 | pages = 7927–32 | date = July 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 Research | volume = 28 | issue = 14 | pages = 2847–54 | date = July 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>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
 
| section_title =
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"/>
| 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==
==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
[[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 = 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 | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = June 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="Vanderweyden">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | date = June 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 | url = http://genomebiology.com/2011/12/6/224 }}</ref><ref name="Dolgin">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | 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 }}</ref><ref name="pmid15340424">{{cite journal | vauthors = Auwerx J, Avner P, Baldock R, Ballabio A, Balling R, Barbacid M, Berns A, Bradley A, Brown S, Carmeliet P, Chambon P, Cox R, Davidson D, Davies K, Duboule D, Forejt J, Granucci F, Hastie N, de Angelis MH, Jackson I, Kioussis D, Kollias G, Lathrop M, Lendahl U, Malumbres M, von Melchner H, Müller W, Partanen J, Ricciardi-Castagnoli P, Rigby P, Rosen B, Rosenthal N, Skarnes B, Stewart AF, Thornton J, Tocchini-Valentini G, Wagner E, Wahli W, Wurst W | title = The European dimension for the mouse genome mutagenesis program | journal = Nature Genetics | volume = 36 | issue = 9 | pages = 925–7 | date = September 2004 | pmid = 15340424 | pmc = 2716028 | doi = 10.1038/ng0904-925 }}</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=
| last1 = Skarnes |first1 =W. C.
Viability at Weaning Data for Rad18 |author=Wellcome Trust Sanger Institute |work=Mouse Resources Portal | publisher = 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 = 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 = www.sanger.ac.uk }}</ref>
| 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>


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* [[Dual-energy X-ray absorptiometry]] (DEXA) showed mutant male mice had a decrease in [[fat]] mass.
* [[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.
* A [[micronucleus test]] found a potential increase in [[DNA damage]] in mutant mice.
A knockout in a human colorectal cancer cell line, HCT116, has also been created.<ref>{{cite journal | vauthors = Shiomi N, Mori M, Tsuji H, Imai T, Inoue H, Tateishi S, Yamaizumi M, Shiomi T | title = Human RAD18 is involved in S phase-specific single-strand break repair without PCNA monoubiquitination | journal = Nucleic Acids Research | volume = 35 | issue = 2 | pages = e9 | date = 2007-01-01 | pmid = 17158148 | doi = 10.1093/nar/gkl979 | url = https://academic.oup.com/nar/article/35/2/e9/2402227 }}</ref>


==Interactions==
== 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==
RAD18 has been shown to [[Protein-protein interaction|interact]] with [[HLTF]],<ref name=pmid18316726>{{cite journal | vauthors = Unk I, Hajdú I, Fátyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L | title = Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 10 | pages = 3768–73 | date = March 2008 | pmid = 18316726 | pmc = 2268824 | doi = 10.1073/pnas.0800563105 }}</ref> [[UBE2B]]<ref name=pmid10884424 /><ref name=pmid10908344 /> and [[UBE2A]].<ref name=pmid10884424/><ref name=pmid10908344/>
{{reflist|2}}
{{clear}}


==Further reading==
== References ==
{{refbegin|35em}}
{{reflist|32}}
{{PBB_Further_reading
 
| citations =
== Further reading ==
*{{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 }}
{{refbegin|32em}}
*{{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 | 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 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{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 | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | 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 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{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 | vauthors = Mulder LC, Chakrabarti LA, Muesing MA | title = Interaction of HIV-1 integrase with DNA repair protein hRad18 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 30 | pages = 27489–93 | date = July 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 | vauthors = Nikiforov AA, Sasina LK, Svetlova MP, Solovjeva LV, Oei SL, Bradbury EM, Tomilin NV | title = Early immobilization of nuclease FEN1 and accumulation of hRAD18 protein at stalled DNA replication forks in mammalian cells | journal = Doklady Biochemistry and Biophysics | volume = 389 | issue =  | pages = 122–5 | year = 2004 | pmid = 12856420 | doi = 10.1023/A:1023696425171 }}
*{{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 | vauthors = Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP | title = Large-scale characterization of HeLa cell nuclear phosphoproteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 33 | pages = 12130–5 | date = August 2004 | pmid = 15302935 | pmc = 514446 | doi = 10.1073/pnas.0404720101 }}
*{{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 | vauthors = Watanabe K, Tateishi S, Kawasuji M, Tsurimoto T, Inoue H, Yamaizumi M | title = Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination | journal = The EMBO Journal | volume = 23 | issue = 19 | pages = 3886–96 | date = October 2004 | pmid = 15359278 | pmc = 522788 | doi = 10.1038/sj.emboj.7600383 }}
*{{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 | vauthors = Nikiforov A, Svetlova M, Solovjeva L, Sasina L, Siino J, Nazarov I, Bradbury M, Tomilin N | title = DNA damage-induced accumulation of Rad18 protein at stalled replication forks in mammalian cells involves upstream protein phosphorylation | journal = Biochemical and Biophysical Research Communications | volume = 323 | issue = 3 | pages = 831–7 | date = October 2004 | pmid = 15381075 | doi = 10.1016/j.bbrc.2004.08.165 }}
*{{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 | vauthors = Miyase S, Tateishi S, Watanabe K, Tomita K, Suzuki K, Inoue H, Yamaizumi M | title = Differential regulation of Rad18 through Rad6-dependent mono- and polyubiquitination | journal = The Journal of Biological Chemistry | volume = 280 | issue = 1 | pages = 515–24 | date = January 2005 | pmid = 15509568 | doi = 10.1074/jbc.M409219200 }}
*{{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 | vauthors = Masuyama S, Tateishi S, Yomogida K, Nishimune Y, Suzuki K, Sakuraba Y, Inoue H, Ogawa M, Yamaizumi M | title = Regulated expression and dynamic changes in subnuclear localization of mammalian Rad18 under normal and genotoxic conditions | journal = Genes to Cells | volume = 10 | issue = 8 | pages = 753–62 | date = August 2005 | pmid = 16098139 | doi = 10.1111/j.1365-2443.2005.00874.x }}
*{{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 | vauthors = Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R | title = Phosphoproteome analysis of the human mitotic spindle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 14 | pages = 5391–6 | date = April 2006 | pmid = 16565220 | pmc = 1459365 | doi = 10.1073/pnas.0507066103 }}
*{{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 | vauthors = Bi X, Barkley LR, Slater DM, Tateishi S, Yamaizumi M, Ohmori H, Vaziri C | title = Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest | journal = Molecular and Cellular Biology | volume = 26 | issue = 9 | pages = 3527–40 | date = May 2006 | pmid = 16611994 | pmc = 1447421 | doi = 10.1128/MCB.26.9.3527-3540.2006 }}
*{{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 | vauthors = Lloyd AG, Tateishi S, Bieniasz PD, Muesing MA, Yamaizumi M, Mulder LC | title = Effect of DNA repair protein Rad18 on viral infection | journal = PLoS Pathogens | volume = 2 | issue = 5 | pages = e40 | date = May 2006 | pmid = 16710452 | pmc = 1463017 | doi = 10.1371/journal.ppat.0020040 }}
*{{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 | vauthors = Yuasa MS, Masutani C, Hirano A, Cohn MA, Yamaizumi M, Nakatani Y, Hanaoka F | 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 to Cells | volume = 11 | issue = 7 | pages = 731–44 | date = July 2006 | pmid = 16824193 | doi = 10.1111/j.1365-2443.2006.00974.x }}
*{{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 | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nature Biotechnology | volume = 24 | issue = 10 | pages = 1285–92 | date = October 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 }}
*{{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 | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = November 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
*{{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   |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 }}
}}
{{refend}}
{{refend}}
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[[Category:Genes mutated in mice]]
[[Category:Genes mutated in mice]]
[[Category:DNA repair]]
[[Category:DNA repair]]

Latest revision as of 15:00, 24 March 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Wikidata
View/Edit Human

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

Function

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]

A knockout in a human colorectal cancer cell line, HCT116, has also been created.[21]

Interactions

RAD18 has been shown to interact with HLTF,[22] 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 (July 2000). "Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens". Proceedings of the National Academy of Sciences of the United States of America. 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 (July 2000). "The human RAD18 gene product interacts with HHR6A and HHR6B". Nucleic Acids Research. 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.
  5. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  6. ↑ 6.0 6.1 van der Weyden L, White JK, Adams DJ, 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 (7351): 262–3. 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, Ballabio A, Balling R, Barbacid M, Berns A, Bradley A, Brown S, Carmeliet P, Chambon P, Cox R, Davidson D, Davies K, Duboule D, Forejt J, Granucci F, Hastie N, de Angelis MH, Jackson I, Kioussis D, Kollias G, Lathrop M, Lendahl U, Malumbres M, von Melchner H, Müller W, Partanen J, Ricciardi-Castagnoli P, Rigby P, Rosen B, Rosenthal N, Skarnes B, Stewart AF, Thornton J, Tocchini-Valentini G, Wagner E, Wahli W, Wurst W (September 2004). "The European dimension for the mouse genome mutagenesis program". Nature Genetics. 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.
  11. ↑ Wellcome Trust Sanger Institute. "Fertility Data for Rad18". Mouse Resources Portal. www.sanger.ac.uk.
  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.
  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. ↑ Shiomi N, Mori M, Tsuji H, Imai T, Inoue H, Tateishi S, Yamaizumi M, Shiomi T (2007-01-01). "Human RAD18 is involved in S phase-specific single-strand break repair without PCNA monoubiquitination". Nucleic Acids Research. 35 (2): e9. doi:10.1093/nar/gkl979. PMID 17158148.
  22. ↑ Unk I, Hajdú I, Fátyol K, Hurwitz J, Yoon JH, Prakash L, Prakash S, Haracska L (March 2008). "Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination". Proceedings of the National Academy of Sciences of the United States of America. 105 (10): 3768–73. doi:10.1073/pnas.0800563105. PMC 2268824. PMID 18316726.

Further reading

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