Artículo
Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability
Autor/es | Lafuente Barquero, Juan Francisco
Svejstrup, Jesper Q. Luna Varo, Rosa María ![]() ![]() ![]() ![]() ![]() ![]() Aguilera López, Andrés ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2024-05-26 |
Fecha de depósito | 2024-06-07 |
Publicado en |
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Resumen | RECQL5 is a member of the conserved RecQ family of DNA helicases involved in the maintenance of genome stability that is specifically found in higher eukaryotes and associates with the elongating RNA polymerase II. To ... RECQL5 is a member of the conserved RecQ family of DNA helicases involved in the maintenance of genome stability that is specifically found in higher eukaryotes and associates with the elongating RNA polymerase II. To expand our understanding of its function we expressed human RECQL5 in the yeast Saccharomyces cerevisiae, which does not have a RECQL5 ortholog. We found that RECQL5 expression leads to cell growth inhibition, increased genotoxic sensitivity and transcription-associated hyperrecombination. Chromatin immunoprecipitation and transcriptomic analysis of yeast cells expressing human RECQL5 shows that this is recruited to transcribed genes and although it causes only a weak impact on gene expression, in particular at G + C-rich genes, it leads to a transcription termination defect detected as readthrough transcription. The data indicate that the interaction between RNAPII and RECQL5 is conserved from yeast to humans. Unexpectedly, however, the RECQL5-ID mutant, previously shown to have reduced the association with RNAPII in vitro, associates with the transcribing polymerase in cells. As a result, expression of RECQL5-ID leads to similar although weaker phenotypes than wild-type RECQL5 that could be transcription-mediated. Altogether, the data suggests that RECQL5 has the intrinsic ability to function in transcription-dependent and independent genome dynamics in S. cerevisiae. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España European Research Council (ERC) Novo Nordisk Foundation Danish National Research Foundation |
Identificador del proyecto | BFU2016-75058-P
![]() ERC2014 AdG669898 TARLOOP ![]() 693327 ![]() NNF19OC0055875 ![]() DNRF153 ![]() |
Cita | Lafuente Barquero, J.F., Svejstrup, J.Q., Luna Varo, R.M. y Aguilera López, A. (2024). Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability. Molecular Genetics and Genomics, 299 (1), 59. https://doi.org/10.1007/s00438-024-02152-3. |
Ficheros | Tamaño | Formato | Ver | Descripción |
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Expression of human RECQL5.pdf | 1.058Mb | ![]() | Ver/ | Versión publicada |