RNA-processing proteins regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA

Autor: Nicola Manfrini, Daniele Cesena, Maxime Wery, Antonin Morillon, Marina Martina, Maria Pia Longhese, Fabrizio d'Adda di Fagagna, Marc Descrimes, Camilla Trovesi
Přispěvatelé: Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Manfrini, N, Trovesi, C, Wery, M, Martina, M, Cesena, D, Descrimes, M, Morillon, A, D'Adda Di Fagagna, F, Longhese, M
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Saccharomyces cerevisiae Proteins
DNA Repair
DNA repair
genetic processes
RAD52
RAD51
DNA
Single-Stranded
BIO/18 - GENETICA
DNA-Directed DNA Polymerase
Saccharomyces cerevisiae
Protein Serine-Threonine Kinases
Biology
Trf4
Biochemistry
DNA damage checkpoint
chemistry.chemical_compound
Genetic
Replication Protein A
Rrp6
Genetics
DNA Breaks
Double-Stranded
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Xrn1
Molecular Biology
Replication protein A
ComputingMilieux_MISCELLANEOUS
Exosome Multienzyme Ribonuclease Complex
Scientific Reports
Intracellular Signaling Peptides and Proteins
G2-M DNA damage checkpoint
Molecular biology
Cell biology
DNA-Binding Proteins
enzymes and coenzymes (carbohydrates)
MRX complex
chemistry
DNA double-strand break
Exoribonucleases
health occupations
biological phenomena
cell phenomena
and immunity
Homologous recombination
DNA
Zdroj: EMBO reports
EMBO Reports
EMBO Reports, EMBO Press, 2014, 16 (2), pp.221-231. ⟨10.15252/embr.201439458⟩
EMBO Reports, 2014, 16 (2), pp.221-231. ⟨10.15252/embr.201439458⟩
ISSN: 1469-221X
1469-3178
DOI: 10.15252/embr.201439458
Popis: Eukaryotic cells respond to DNA double-strand breaks (DSBs) by activating a checkpoint that depends on the protein kinases Tel1/ATM and Mec1/ATR. Mec1/ATR is activated by RPA-coated single-stranded DNA (ssDNA), which arises upon nucleolytic degradation (resection) of the DSB. Emerging evidences indicate that RNA-processing factors play critical, yet poorly understood, roles in genomic stability. Here, we provide evidence that the Saccharomyces cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 regulate Mec1/ATR activation by promoting generation of RPA-coated ssDNA. The lack of Xrn1 inhibits ssDNA generation at the DSB by preventing the loading of the MRX complex. By contrast, DSB resection is not affected in the absence of Rrp6 or Trf4, but their lack impairs the recruitment of RPA, and therefore of Mec1, to the DSB. Rrp6 and Trf4 inactivation affects neither Rad51/Rad52 association nor DSB repair by homologous recombination (HR), suggesting that full Mec1 activation requires higher amount of RPA-coated ssDNA than HR-mediated repair. Noteworthy, deep transcriptome analyses do not identify common misregulated gene expression that could explain the observed phenotypes. Our results provide a novel link between RNA processing and genome stability. Synopsis The S. cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 facilitate Mec1/ATR activation by promoting the formation of RPA-coated ssDNA at dsDNA breaks. Xrn1 promotes the formation of single-stranded DNA at the ends of double-stranded DNA breaks. Rrp6 and Trf4 contribute to the recruitment of RPA and Mec1/ATR to the single-stranded DNA ends. The S. cerevisiae RNA decay factors Xrn1, Rrp6 and Trf4 facilitate Mec1/ATR activation by promoting the formation of RPA-coated ssDNA at dsDNA breaks.
Databáze: OpenAIRE
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