ATP-dependent helicase activity is dispensable for the physiological functions of Recql4.
Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by skin rash (poikiloderma), skeletal dysplasia, small stature, juvenile cataracts, sparse or absent hair, and predisposition to specific malignancies such as osteosarcoma and hematological neoplasms. RTS is caused...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1008266 |
| _version_ | 1818716611404627968 |
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| author | Wilson Castillo-Tandazo Monique F Smeets Vincent Murphy Rui Liu Charlotte Hodson Jörg Heierhorst Andrew J Deans Carl R Walkley |
| author_facet | Wilson Castillo-Tandazo Monique F Smeets Vincent Murphy Rui Liu Charlotte Hodson Jörg Heierhorst Andrew J Deans Carl R Walkley |
| author_sort | Wilson Castillo-Tandazo |
| collection | DOAJ |
| description | Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by skin rash (poikiloderma), skeletal dysplasia, small stature, juvenile cataracts, sparse or absent hair, and predisposition to specific malignancies such as osteosarcoma and hematological neoplasms. RTS is caused by germ-line mutations in RECQL4, a RecQ helicase family member. In vitro studies have identified functions for the ATP-dependent helicase of RECQL4. However, its specific role in vivo remains unclear. To determine the physiological requirement and the biological functions of Recql4 helicase activity, we generated mice with an ATP-binding-deficient knock-in mutation (Recql4K525A). Recql4K525A/K525A mice were strikingly normal in terms of embryonic development, body weight, hematopoiesis, B and T cell development, and physiological DNA damage repair. However, mice bearing two distinct truncating mutations Recql4G522Efs and Recql4R347*, that abolished not only the helicase but also the C-terminal domain, developed a profound bone marrow failure and decrease in survival similar to a Recql4 null allele. These results demonstrate that the ATP-dependent helicase activity of Recql4 is not essential for its physiological functions and that other domains might contribute to this phenotype. Future studies need to be performed to elucidate the complex interactions of RECQL4 domains and its contribution to the development of RTS. |
| first_indexed | 2024-12-17T19:22:01Z |
| format | Article |
| id | doaj.art-01bd7b3d2de84365b18d2557fe19cc5a |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-17T19:22:01Z |
| publishDate | 2019-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-01bd7b3d2de84365b18d2557fe19cc5a2022-12-21T21:35:28ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042019-07-01157e100826610.1371/journal.pgen.1008266ATP-dependent helicase activity is dispensable for the physiological functions of Recql4.Wilson Castillo-TandazoMonique F SmeetsVincent MurphyRui LiuCharlotte HodsonJörg HeierhorstAndrew J DeansCarl R WalkleyRothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by skin rash (poikiloderma), skeletal dysplasia, small stature, juvenile cataracts, sparse or absent hair, and predisposition to specific malignancies such as osteosarcoma and hematological neoplasms. RTS is caused by germ-line mutations in RECQL4, a RecQ helicase family member. In vitro studies have identified functions for the ATP-dependent helicase of RECQL4. However, its specific role in vivo remains unclear. To determine the physiological requirement and the biological functions of Recql4 helicase activity, we generated mice with an ATP-binding-deficient knock-in mutation (Recql4K525A). Recql4K525A/K525A mice were strikingly normal in terms of embryonic development, body weight, hematopoiesis, B and T cell development, and physiological DNA damage repair. However, mice bearing two distinct truncating mutations Recql4G522Efs and Recql4R347*, that abolished not only the helicase but also the C-terminal domain, developed a profound bone marrow failure and decrease in survival similar to a Recql4 null allele. These results demonstrate that the ATP-dependent helicase activity of Recql4 is not essential for its physiological functions and that other domains might contribute to this phenotype. Future studies need to be performed to elucidate the complex interactions of RECQL4 domains and its contribution to the development of RTS.https://doi.org/10.1371/journal.pgen.1008266 |
| spellingShingle | Wilson Castillo-Tandazo Monique F Smeets Vincent Murphy Rui Liu Charlotte Hodson Jörg Heierhorst Andrew J Deans Carl R Walkley ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. PLoS Genetics |
| title | ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. |
| title_full | ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. |
| title_fullStr | ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. |
| title_full_unstemmed | ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. |
| title_short | ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. |
| title_sort | atp dependent helicase activity is dispensable for the physiological functions of recql4 |
| url | https://doi.org/10.1371/journal.pgen.1008266 |
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