skip to primary navigationskip to content
 

19.09.16 Fine details teased out in pathway of DNA repair by homologous recombination

last modified Oct 25, 2016 10:32 AM
Steve Jackson's lab pin down further events in the DNA repair pathway in this Nature Communications paper
19.09.16 Fine details teased out in pathway of DNA repair by homologous recombination

Excerpt from Fig. 5e in the paper: proposed model for repair of single-ended DNA double-strand breaks

Coordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks

Chanut P, Britton S, Coates J, Jackson SP, Calsou P. Nat Commun. (2016) 7:12889 DOI 10.1038/ncomms12889    [PMID: 27641979]

 

Abstract from the paper:

Repair of single-ended DNA double-strand breaks (seDSBs) by homologous recombination (HR) requires the generation of a 3' single-strand DNA overhang by exonuclease activities in a process called DNA resection. However, it is anticipated that the highly abundant DNA end-binding protein Ku sequesters seDSBs and shields them from exonuclease activities. Despite pioneering works in yeast, it is unclear how mammalian cells counteract Ku at seDSBs to allow HR to proceed. Here we show that in human cells, ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on seDSBs. We also provide evidence for a hitherto unsuspected additional mechanism that contributes to prevent Ku accumulation at seDSBs, acting downstream of MRE11 endonuclease activity and in parallel with MRE11 exonuclease activity. Finally, we show that Ku persistence at seDSBs compromises Rad51 focus assembly but not DNA resection.

 

Abstract and figure reproduced under Creative Commons CC BY 4.0.

 

Read more about research in the Jackson lab.

Watch Steve Jackson describe his research on video.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

combinedLogo x3 trans2018

 

Share this

Immune Cell Dynamics Unfolded by Single-Cell Technologies

Chromatin Accessibility Impacts Transcriptional Reprogramming in Oocytes

Integrin α2 marks a niche of trophoblast progenitor cells in first trimester human placenta

Inhibition of the acetyltransferase NAT10 normalizes progeric and aging cells by rebalancing the Transportin-1 nuclear import pathway

SLAM-ITseq: Sequencing cell type-specific transcriptomes without cell sorting

SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements

scmap: projection of single-cell RNA-seq data across data sets

Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis

Map of synthetic rescue interactions for the Fanconi anemia DNA repair pathway identifies USP48

The developmental origin of brain tumours: a cellular and molecular framework

Bioinformatics challenges and perspectives when studying the effect of epigenetic modifications on alternative splicing

ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks

Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer's Disease Disrupt Synaptic Plasticity

Combinational Treatment of Trichostatin A and Vitamin C Improves the Efficiency of Cloning Mice by Somatic Cell Nuclear Transfer

Predominant Asymmetrical Stem Cell Fate Outcome Limits the Rate of Niche Succession in Human Colonic Crypts

G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Link to full list on PubMed