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Series GSE233549 Query DataSets for GSE233549
Status Public on Feb 22, 2024
Title Dbf4-dependent kinase promotes cell-cycle controlled resection of DNA double strand breaks and repair by homologous recombination
Organism Saccharomyces cerevisiae
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary DNA double-strand breaks (DSBs) can be repaired by several pathways. In eukaryotes, repair pathway choice – the cellular decision making underlying DSB repair – occurs at the level of DSB resection and is controlled by the cell cycle. Upon cell cycle-dependent activation, cyclin-dependent kinases (CDKs) phosphorylate resection proteins and thereby stimulate DSB resection and repair by homologous recombination (HR). Here, we identify Dbf4-dependent kinase (DDK) as a second major cell cycle regulator of DNA end resection. Using inducible genetic and chemical inhibition of DDK in budding yeast and human cells, we show that DNA resection and HR require activation by DDK. Mechanistically, DDK catalyzes phosphorylation of at least two resection nucleases. Via phosphorylation of the Mre11 activator Sae2 it promotes activation of resection initiation, via phosphorylation of the Dna2 nuclease it promotes long-range resection. Notably, synthetic activiation of DDK allows limited resection and HR in G1 cells, suggesting that DDK is a key component of DSB repair decision making.
 
Overall design Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for Replication Protein A (RPA) in different Saccharomyces cerevisiae strains: WT, dbf4-3AID, sae2-S267E, GAL-DDK, sae2-S267E GAL-DDK. N ≥ 2 replicates
 
Contributor(s) Galanti L, Peritore M, Gnügge R, Cannavó E, Palumbieri M, Steigenberger B, Symington LS, Cejka P, Pfander B
Citation(s) 38570537
Submission date May 26, 2023
Last update date Apr 17, 2024
Contact name Martina Peritore
E-mail(s) peritore@biochem.mpg.de
Phone +49 8985783049
Organization name MPIB
Lab Pfander
Street address Am Klopferspitz 18
City Planegg-Martinsried
State/province Bayern
ZIP/Postal code 82152
Country Germany
 
Platforms (2)
GPL19756 Illumina NextSeq 500 (Saccharomyces cerevisiae)
GPL27812 Illumina NovaSeq 6000 (Saccharomyces cerevisiae)
Samples (96)
GSM7430069 YLG135, mock, input, 0h, rep1
GSM7430070 YLG135, mock, input, 2h, rep1
GSM7430071 YLG135, mock, input, 4h, rep1
Relations
BioProject PRJNA976649

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE233549_RAW.tar 3.1 Gb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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