Structural and functional implication of RAP80 ΔGlu81 mutation.
Receptor Associated Protein 80 (RAP80) is a member of RAP80-BRCA1-CCDC98 complex family and helps in its recruitment to the DNA damage site for effective homologous recombination repair. It encompasses two tandem UIMs (UIM1 and UIM2) motif at its N-terminus, which interact with K-63 linked polyubiqu...
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2013
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oai:doaj.org-article:a16b3b7723584d8f874ae92fca9099a92021-11-18T08:56:23ZStructural and functional implication of RAP80 ΔGlu81 mutation.1932-620310.1371/journal.pone.0072707https://doaj.org/article/a16b3b7723584d8f874ae92fca9099a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24039796/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Receptor Associated Protein 80 (RAP80) is a member of RAP80-BRCA1-CCDC98 complex family and helps in its recruitment to the DNA damage site for effective homologous recombination repair. It encompasses two tandem UIMs (UIM1 and UIM2) motif at its N-terminus, which interact with K-63 linked polyubiquitin chain(s) on H2AX and thereby assemble the RAP80-BRCA1 complex at the damage site. Nevertheless, how RAP80 helps in the structural integrity of BRCA1 complex is still elusive. Considering the role of RAP80 in the recruitment of BRCA1 complex at the DNA damage site, we attempted to explore the molecular mechanism associated with RAP80 and mutation that causes chromosomal aberrations due to its loss of function. There is a significant loss in structural characteristics of RAP80 ΔE81, which impairs its binding affinity with the polyubiquitin chain. This leads to the defective recruitment of RAP80 and BRCA1 complex at the DNA damage site. The results presented here are very useful in understanding the cause of various repair defects (chromosomal aberration) that arise due to this mutation. Comparative study of wild type and ΔE81 could be helpful in designing the small molecules that can potentially compensate the deleterious effect(s) of ΔE81 and hence useful for therapeutic application.VikrantRajan KumarLumbini R YadavPallavi NakhwaSanjeev K WaghmarePeyush GoyalAshok K VarmaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e72707 (2013) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Vikrant Rajan Kumar Lumbini R Yadav Pallavi Nakhwa Sanjeev K Waghmare Peyush Goyal Ashok K Varma Structural and functional implication of RAP80 ΔGlu81 mutation. |
| description |
Receptor Associated Protein 80 (RAP80) is a member of RAP80-BRCA1-CCDC98 complex family and helps in its recruitment to the DNA damage site for effective homologous recombination repair. It encompasses two tandem UIMs (UIM1 and UIM2) motif at its N-terminus, which interact with K-63 linked polyubiquitin chain(s) on H2AX and thereby assemble the RAP80-BRCA1 complex at the damage site. Nevertheless, how RAP80 helps in the structural integrity of BRCA1 complex is still elusive. Considering the role of RAP80 in the recruitment of BRCA1 complex at the DNA damage site, we attempted to explore the molecular mechanism associated with RAP80 and mutation that causes chromosomal aberrations due to its loss of function. There is a significant loss in structural characteristics of RAP80 ΔE81, which impairs its binding affinity with the polyubiquitin chain. This leads to the defective recruitment of RAP80 and BRCA1 complex at the DNA damage site. The results presented here are very useful in understanding the cause of various repair defects (chromosomal aberration) that arise due to this mutation. Comparative study of wild type and ΔE81 could be helpful in designing the small molecules that can potentially compensate the deleterious effect(s) of ΔE81 and hence useful for therapeutic application. |
| format |
article |
| author |
Vikrant Rajan Kumar Lumbini R Yadav Pallavi Nakhwa Sanjeev K Waghmare Peyush Goyal Ashok K Varma |
| author_facet |
Vikrant Rajan Kumar Lumbini R Yadav Pallavi Nakhwa Sanjeev K Waghmare Peyush Goyal Ashok K Varma |
| author_sort |
Vikrant |
| title |
Structural and functional implication of RAP80 ΔGlu81 mutation. |
| title_short |
Structural and functional implication of RAP80 ΔGlu81 mutation. |
| title_full |
Structural and functional implication of RAP80 ΔGlu81 mutation. |
| title_fullStr |
Structural and functional implication of RAP80 ΔGlu81 mutation. |
| title_full_unstemmed |
Structural and functional implication of RAP80 ΔGlu81 mutation. |
| title_sort |
structural and functional implication of rap80 δglu81 mutation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/a16b3b7723584d8f874ae92fca9099a9 |
| work_keys_str_mv |
AT vikrant structuralandfunctionalimplicationofrap80dglu81mutation AT rajankumar structuralandfunctionalimplicationofrap80dglu81mutation AT lumbiniryadav structuralandfunctionalimplicationofrap80dglu81mutation AT pallavinakhwa structuralandfunctionalimplicationofrap80dglu81mutation AT sanjeevkwaghmare structuralandfunctionalimplicationofrap80dglu81mutation AT peyushgoyal structuralandfunctionalimplicationofrap80dglu81mutation AT ashokkvarma structuralandfunctionalimplicationofrap80dglu81mutation |
| _version_ |
1718421157538955264 |