A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?

Simple item page
dc.contributor.authorZhao, Xiao-Nanen_ZA
dc.contributor.authorLokanga, Rachelen_ZA
dc.contributor.authorAllette, Kimaadaen_ZA
dc.contributor.authorGazy, Inbalen_ZA
dc.contributor.authorWu, Dien_ZA
dc.contributor.authorUsdin, Karenen_ZA
dc.date.accessioned2016-10-31T07:41:44Z
dc.date.available2016-10-31T07:41:44Z
dc.date.issued2016en_ZA
dc.description.abstractAuthor Summary: The repeat expansion diseases are a group of human genetic disorders that are caused by expansion of a specific microsatellite in a single affected gene. How this expansion occurs is unknown, but previous work in various models for different diseases in the group, including the fragile X-related disorders (FXDs), has implicated the mismatch repair complex MutSβ in the process. With the exception of somatic expansion in Friedreich ataxia, MutSα has not been reported to contribute to generation of expansions in other disease models. Here we show that MutSα does in fact play a role in both germ line and somatic expansions in a mouse model of the FXDs since the expansion frequency is significantly reduced in Msh6 -/- mice. However, since we have previously shown that loss of MutSβ eliminates almost all expansions, MutSα is apparently not able to fully substitute for MutSβ in the expansion process. We also show here that MutSα increases the stability of the structures formed by the fragile X repeats that are thought to be the substrates for expansion and promotes binding of MutSβ to the repeats. This, together with our genetic data, suggests possible models for how MutSα and MutSβ, could co-operate to generate repeat expansions in the FXDs.en_ZA
dc.identifier.apacitationZhao, X., Lokanga, R., Allette, K., Gazy, I., Wu, D., & Usdin, K. (2016). A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?. <i>PLOS Genetics</i>, http://hdl.handle.net/11427/22371en_ZA
dc.identifier.chicagocitationZhao, Xiao-Nan, Rachel Lokanga, Kimaada Allette, Inbal Gazy, Di Wu, and Karen Usdin "A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?." <i>PLOS Genetics</i> (2016) http://hdl.handle.net/11427/22371en_ZA
dc.identifier.citationZhao, X. N., Lokanga, R., Allette, K., Gazy, I., Wu, D., & Usdin, K. (2016). A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?. PLoS Genet, 12(7), e1006190. doi:10.1371/journal.pgen.1006190en_ZA
dc.identifier.ris TY - Journal Article AU - Zhao, Xiao-Nan AU - Lokanga, Rachel AU - Allette, Kimaada AU - Gazy, Inbal AU - Wu, Di AU - Usdin, Karen AB - Author Summary: The repeat expansion diseases are a group of human genetic disorders that are caused by expansion of a specific microsatellite in a single affected gene. How this expansion occurs is unknown, but previous work in various models for different diseases in the group, including the fragile X-related disorders (FXDs), has implicated the mismatch repair complex MutSβ in the process. With the exception of somatic expansion in Friedreich ataxia, MutSα has not been reported to contribute to generation of expansions in other disease models. Here we show that MutSα does in fact play a role in both germ line and somatic expansions in a mouse model of the FXDs since the expansion frequency is significantly reduced in Msh6 -/- mice. However, since we have previously shown that loss of MutSβ eliminates almost all expansions, MutSα is apparently not able to fully substitute for MutSβ in the expansion process. We also show here that MutSα increases the stability of the structures formed by the fragile X repeats that are thought to be the substrates for expansion and promotes binding of MutSβ to the repeats. This, together with our genetic data, suggests possible models for how MutSα and MutSβ, could co-operate to generate repeat expansions in the FXDs. DA - 2016 DB - OpenUCT DO - 10.1371/journal.pgen.1006190 DP - University of Cape Town J1 - PLOS Genetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice? TI - A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice? UR - http://hdl.handle.net/11427/22371 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pgen.1006190en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22371
dc.identifier.vancouvercitationZhao X, Lokanga R, Allette K, Gazy I, Wu D, Usdin K. A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?. PLOS Genetics. 2016; http://hdl.handle.net/11427/22371.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Geneticsen_ZA
dc.source.urihttp://journals.plos.org/plosgeneticsen_ZA
dc.subject.otherMouse modelsen_ZA
dc.subject.otherPolymerase chain reactionen_ZA
dc.subject.otherSpermen_ZA
dc.subject.otherOligonucleotidesen_ZA
dc.subject.otherProtein extractionen_ZA
dc.subject.otherDNA-binding proteinsen_ZA
dc.subject.otherGenotypingen_ZA
dc.subject.otherTestesen_ZA
dc.titleA MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice?en_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Zhao_A_MutSB_Dependent_Contribution_of_Muta_2016.pdf
Size:
1.51 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles