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 -
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en_ZA |