دورية أكاديمية
DICER ribonuclease removes harmful R-loops
| العنوان: | DICER ribonuclease removes harmful R-loops |
|---|---|
| المؤلفون: | Camino, Lola P., Dutta, Arijit, Barroso, Sonia, Pérez-Calero, Carmen, Katz, Jeffrey N., García-Rubio, María, Sung, Patrick, Gómez-González, Belén, Aguilera, Andrés |
| المساهمون: | Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), European Research Council, European Commission, Fundación Vencer el Cancer, National Institutes of Health (US), Grayce B. Kerr Fund, Asociación Española Contra el Cáncer, Welch Foundation, Yale University, University of Texas at San Antonio |
| بيانات النشر: | Cell Press Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | DICER, DICER1 syndrome, DNA damage, R-loops, RNA nuclease, Genetic instability, Replication fork stalling |
| الوصف: | R-loops, which consist of a DNA-RNA hybrid and a displaced DNA strand, are known to threaten genome integrity. To counteract this, different mechanisms suppress R-loop accumulation by either preventing the hybridization of RNA with the DNA template (RNA biogenesis factors), unwinding the hybrid (DNA-RNA helicases), or degrading the RNA moiety of the R-loop (type H ribonucleases [RNases H]). Thus far, RNases H are the only nucleases known to cleave DNA-RNA hybrids. Now, we show that the RNase DICER also resolves R-loops. Biochemical analysis reveals that DICER acts by specifically cleaving the RNA within R-loops. Importantly, a DICER RNase mutant impaired in R-loop processing causes a strong accumulation of R-loops in cells. Our results thus not only reveal a function of DICER as an R-loop resolvase independent of DROSHA but also provide evidence for the role of multi-functional RNA processing factors in the maintenance of genome integrity in higher eukaryotes. ; Research was part of the project I+D+i PID2019-104270GB-I00/BMC, funded by MCIN/AEI/10.13039/501100011033/ to A.A., as a main funding source, plus grants from the European Research Council (ERC2014 AdG669898 TARLOOP) and Foundation “Vencer el Cancer” to A.A. and NIH grants RO1 ES007061, RO1 CA168635, and R35CA241801 and a Gray Foundation Team Science Award under the Basser BRCA Initiative to P.S. P.S. is the holder of the Robert A. Welch Distinguished Chair in Chemistry (AQ-0012) and the Greehey Distinguished Chair. B.G.-G. was the recipient of a contract from the Asociación Española Contra el Cancer (AECC). A.D. was supported by a 2018 Brown-Coxe postdoctoral fellowship from Yale University, a 2019 Jean B. Kempner postdoctoral fellowship from University of Texas Medical Branch at Galveston, TX, and a 2020 OPA/SALSI fellowship from UT Health San Antonio, TX. We thank Youngho Kwon for technical advice. We thank B. Bass and J. Doudna for kindly providing pFastBac-OSF-hDICER and pFastBac-hDcr constructs, respectively. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1097-2765 1097-4164 |
| العلاقة: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104270GB-I00/ES/MECANISMOS DE INESTABILIDAD GENOMICA MEDIADA POR ARN Y REPARACION/; Molecular cell; The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1016/j.molcel.2023.09.021Test; https://doi.org/10.1016/j.molcel.2023.09.021Test; Sí; Molecular Cell 83(20): 3707-3719.e5 (2023); http://hdl.handle.net/10261/346917Test; http://dx.doi.org/10.13039/100005326Test; http://dx.doi.org/10.13039/100000002Test; http://dx.doi.org/10.13039/100008634Test; http://dx.doi.org/10.13039/100000928Test; http://dx.doi.org/10.13039/501100011033Test; http://dx.doi.org/10.13039/501100000780Test; http://dx.doi.org/10.13039/501100000781Test; 2-s2.0-85174000211; https://api.elsevier.com/content/abstract/scopus_id/85174000211Test |
| DOI: | 10.1016/j.molcel.2023.09.021 |
| DOI: | 10.13039/100005326 |
| DOI: | 10.13039/100000002 |
| DOI: | 10.13039/100008634 |
| DOI: | 10.13039/100000928 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100000780 |
| DOI: | 10.13039/501100000781 |
| الإتاحة: | https://doi.org/10.1016/j.molcel.2023.09.02110.13039/10000532610.13039/10000000210.13039/10000863410.13039/10000092810.13039/50110001103310.13039/50110000078010.13039/501100000781Test http://hdl.handle.net/10261/346917Test https://api.elsevier.com/content/abstract/scopus_id/85174000211Test |
| حقوق: | none |
| رقم الانضمام: | edsbas.DA9A801 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10972765 10974164 |
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| DOI: | 10.1016/j.molcel.2023.09.021 |