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| Open AccessSelective removal of deletion-bearing mitochondrial DNA in heteroplasmic Drosophila
Heteroplasmy, in which mutant and wild-type mitochondrial DNA (mtDNA) coexist in a cell, can result in diseases. Here the authors generate transgenic flies with heteroplasmic mtDNA in flight muscles, and show that stimulation of autophagy, or a decrease in mitofusin, promotes clearance of mutant mtDNA.
- Nikolay P. Kandul
- , Ting Zhang
- & Ming Guo
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Article
| Open AccessClassical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes
Most adult mammalian cells prefer to repair double-strand DNA breaks though the classical nonhomologous end-joining pathway. Here the authors present evidence that a nascent RNA transcript can serve as a template to facilitate error-free repair.
- Anirban Chakraborty
- , Nisha Tapryal
- & Tapas K. Hazra
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| Open AccessCoordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks
Homologous recombination requires end resection of the DNA at the site of the break, however the Ku dimer can sequester single-ended double-strand breaks. Here the authors show that ATM-dependent phosphorylation of CtIP, along with the actions of Mre11, impair the stable loading of Ku onto DNA.
- Pauline Chanut
- , Sébastien Britton
- & Patrick Calsou
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Article
| Open AccessDNA transposon activity is associated with increased mutation rates in genes of rice and other grasses
DNA transposons are numerous in plant genomes. Here, Wicker et al. analyse transposon polymorphisms in rice and other grasses and show that sequences flanking excision sites contain up to 10 times more mutations than average, suggesting transposons are a major factor shaping the evolution of grass genomes.
- Thomas Wicker
- , Yeisoo Yu
- & Stefan Roffler
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| Open AccessA genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection
A DNA double strand break can be repaired through either the non-homologous end-joining or the homologous recombination pathways. Here the authors conduct a genome-wide screen and identify a role for CCAR2 in pathway choice by regulating DNA end resection by CtIP.
- Ana López-Saavedra
- , Daniel Gómez-Cabello
- & Pablo Huertas
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Article
| Open AccessSIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability
SIRT7 is a member of sirtuin family proteins that are described as NAD+-dependent class III histone deacetylases. Here, the authors show that SIRT7 is histone desuccinylase catalysing H3K122 desuccinylation, thereby promoting chromatin condensation and repair of DNA double strand breaks.
- Lei Li
- , Lan Shi
- & Wenhua Yu
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| Open AccessCRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection
The repair of double-strand DNA breaks by homologous recombination requires resection of the DNA ends. Here the authors show that in Schizosaccharomyces pombe and human cells, Wdr70 is recruited as part of the CRL4 complex to promote ubiquitination of H2B and allow Exo1-mediated resection.
- Ming Zeng
- , Laifeng Ren
- & Cong Liu
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Article
| Open AccessRAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair
Antigen receptor diversity relies on careful DNA cleavage and repair. Here the authors identify a functional interplay between RAG2 and XLF during V(D)J recombination, revealing an important role for the RAG complex in repairing induced DNA double-strand breaks and maintaining genome integrity.
- Chloé Lescale
- , Vincent Abramowski
- & Ludovic Deriano
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Article
| Open AccessInactivation of nuclear GSK3β by Ser389 phosphorylation promotes lymphocyte fitness during DNA double-strand break response
Double stranded DNA breaks are generated during rearrangements of lymphocyte antigen receptors. Here the authors show that the DNA breaks induce phosphorylation of nuclear GSK3β at Ser389/Thr390, protecting the activated lymphocytes from necroptosis-mediated cell death.
- Tina M. Thornton
- , Pilar Delgado
- & Mercedes Rincón
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| Open AccessA cell cycle-dependent BRCA1–UHRF1 cascade regulates DNA double-strand break repair pathway choice
BRCA1 is a key regulator of DNA double-strand break repair, functioning to promote homologous recombination and repress non-homologous end-joining. Here the authors show that the ubiquitin ligase UHRF1 is recruited to breaks by BRCA1, where it targets RIF1 and thereby facilitates recombination.
- Haoxing Zhang
- , Hailong Liu
- & Huadong Pei
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Article
| Open AccessMCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1 complex
The MCM8-9 complex is required for repair of DNA double-strand breaks (DSBs). Here, the authors show that MCM8-9 is required for the nuclease activity of the MRE11-RAD50-NBS1 complex (MRN) and stabilizes its association with DNA damage sites, promoting resection of DSB ends.
- Kyung Yong Lee
- , Jun-Sub Im
- & Anindya Dutta
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Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process
Damaged DNA is often targeted to nuclear pore complexes for repair. Here, the authors show that kinesin-14 mediates this process ensuring error-prone repair, while perinuclear telomere attachment licenses damaged telomeric loci for this repair and kinesin-14 blocks senescence in the absence of telomerase.
- Daniel K.C. Chung
- , Janet N.Y. Chan
- & Karim Mekhail
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Article
| Open AccessPolymerase Θ is a key driver of genome evolution and of CRISPR/Cas9-mediated mutagenesis
DNA double-stranded breaks can be repaired through error-prone pathways. Here, van Schendel et al. demonstrate that C. elegansacquires inheritable mutations through the use of polymerase theta-mediated end joining.
- Robin van Schendel
- , Sophie F. Roerink
- & Marcel Tijsterman
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Elucidation of IgH 3′ region regulatory role during class switch recombination via germline deletion
The molecular mechanisms of antibody class switching are incompletely understood. Here the authors show by using mice specifically lacking the IgH 3′ regulatory region enhancers that they prime the first steps of the class switch recombination.
- Alexis Saintamand
- , Pauline Rouaud
- & Yves Denizot
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| Open AccessControlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing
Accumulation of DNA damage is a hallmark of cellular ageing but cause and effect are unclear. Here White et al.induce clean DNA double-strand breaks in the liver of mice using a modified restriction enzyme and demonstrate that DNA damage alone is sufficient to recapitulate some aspects of tissue ageing.
- Ryan R. White
- , Brandon Milholland
- & Jan Vijg
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| Open AccessInteractome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway
DNA double-strand breaks (DSBs), a highly deleterious form of DNA damage, are associated with multiple types of broken ends. Here, the authors identify a XRCC4-like factor that functions in the non-homologous end-joining DNA repair pathway to repair DSBs with complex broken ends.
- Mengtan Xing
- , Mingrui Yang
- & Dongyi Xu
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Cell transcriptional state alters genomic patterns of DNA double-strand break repair in human astrocytes
Misrepair of DNA double-strand breaks can lead to chromosomal rearrangements, which can promote carcinogenesis. Here, the authors show in cultured human astrocytes that transcriptional activation impacts on DNA double-strand break formation and repair upon ionizing radiation in a site-specific manner.
- Raymund L. Yong
- , Chunzhang Yang
- & Russell R. Lonser
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An RNA polymerase II-coupled function for histone H3K36 methylation in checkpoint activation and DSB repair
Chromatin modifications play a fundamental role in regulating the cellular response to DNA damage. Here, Jha and Strahl identify methylation of histone H3 on lysine 36 mediated by the histone-methyltransferase Set2 as a regulator of chromatin remodelling at double-strand breaks that affects DNA repair.
- Deepak Kumar Jha
- & Brian D. Strahl
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A histone H3K36 chromatin switch coordinates DNA double-strand break repair pathway choice
DNA double strand breaks are repaired by nonhomologous end-joining (NHEJ) or homologous recombination (HR) pathways. Here, Pai et al.discover that post-translational modification of lysine 36 of histone H3 plays a key role in determining double strand repair pathway choice.
- Chen-Chun Pai
- , Rachel S. Deegan
- & Timothy C. Humphrey
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| Open AccessATM specifically mediates repair of double-strand breaks with blocked DNA ends
The role of ATM in DNA double-strand break (DSB) signalling is well established, but its function in the repair process remains controversial. Here, Álvarez-Quilón et al.show that ATM acts in the joining of blocked DSBs, uncovering DNA end structure as a key factor determining ATM involvement in DSB repair.
- Alejandro Álvarez-Quilón
- , Almudena Serrano-Benítez
- & Felipe Cortés-Ledesma
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DNA repair choice defines a common pathway for recruitment of chromatin regulators
Chromatin regulators facilitate repair of DNA double-strand breaks in chromosomal DNA. The authors show that the recruitment of such chromatin regulators to DNA lesions is controlled by the choice of DNA repair pathway.
- Gwendolyn Bennett
- , Manolis Papamichos-Chronakis
- & Craig L. Peterson
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FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress
DNA replication stress promotes genome instability and cell death. Here Fugger et al.describe how FBH1, via its helicase activity, is required to eliminate cells with excessive DNA replication stress, through the generation of MUS81-induced DNA double-strand breaks.
- Kasper Fugger
- , Wai Kit Chu
- & Claus Storgaard Sørensen
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FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage
The protein ataxia-telangiectasia mutated (ATM) detects DNA damage and can trigger cellular apoptosis, but how this process is regulated at the molecular level is unclear. Here, Chunget al. show that the transcription factor FOXO3 controls the formation of ATM-containing signalling complexes at sites of DNA damage that trigger apoptosis.
- Young Min Chung
- , See-Hyoung Park
- & Mickey C.-T. Hu