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

 

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dc.contributor.author Zhao, Xiao-Nan en_ZA
dc.contributor.author Lokanga, Rachel en_ZA
dc.contributor.author Allette, Kimaada en_ZA
dc.contributor.author Gazy, Inbal en_ZA
dc.contributor.author Wu, Di en_ZA
dc.contributor.author Usdin, Karen en_ZA
dc.date.accessioned 2016-10-31T07:41:44Z
dc.date.available 2016-10-31T07:41:44Z
dc.date.issued 2016 en_ZA
dc.identifier.citation Zhao, 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.1006190 en_ZA
dc.identifier.uri http://dx.doi.org/10.1371/journal.pgen.1006190 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/22371
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLOS Genetics en_ZA
dc.source.uri http://journals.plos.org/plosgenetics en_ZA
dc.subject.other Mouse models en_ZA
dc.subject.other Polymerase chain reaction en_ZA
dc.subject.other Sperm en_ZA
dc.subject.other Oligonucleotides en_ZA
dc.subject.other Protein extraction en_ZA
dc.subject.other DNA-binding proteins en_ZA
dc.subject.other Genotyping en_ZA
dc.subject.other Testes en_ZA
dc.title A MutSβ-Dependent Contribution of MutSα to Repeat Expansions in Fragile X Premutation Mice? en_ZA
dc.type Journal Article en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Medical Biochemistry en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Zhao, 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/11427/22371 en_ZA
dc.identifier.chicagocitation Zhao, 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/11427/22371 en_ZA
dc.identifier.vancouvercitation Zhao 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.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


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This 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. Except where otherwise noted, this item's license is described as This 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.