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| Open AccessA replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells
Origins of mammalian DNA replication are poorly characterised because they lack an Identifiable consensus sequence. Here the authors identify RepID, a protein that binds to a subset of G-rich replication origins and facilitates initiation from those origins.
- Ya Zhang
- , Liang Huang
- & Mirit I. Aladjem
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| Open AccessMechanical cell competition kills cells via induction of lethal p53 levels
Cell competition is a quality control mechanism to eliminate unfit cells. Here the authors show that physical compaction of less fit cells surrounded by healthy neighbours leads to increased expression of tumour suppressor p53 in the compacted cells, causing cell death.
- Laura Wagstaff
- , Maja Goschorska
- & Eugenia Piddini
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| Open AccessThe Ku-binding motif is a conserved module for recruitment and stimulation of non-homologous end-joining proteins
Werner syndrome is a progeroid disease characterised by genetic instability due to mutations to the WRN helicase/exonuclease. Here the authors define a novel Ku binding motif (KBM) and show that two such motifs facilitate the involvement of WRN in DNA double-strand break repair.
- Gabrielle J. Grundy
- , Stuart L. Rulten
- & Keith W. Caldecott
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Article
| Open AccessSCFSAP controls organ size by targeting PPD proteins for degradation in Arabidopsis thaliana
Organ size in plants is regulated by cell proliferation and cell expansion. Here, Wang et al. show that STERILE APETALA participates in the regulation of organ size as a component of an E3 ligase complex that promotes the degradation of negative regulators of meristemoid proliferation
- Zhibiao Wang
- , Na Li
- & Yunhai Li
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Article
| Open AccessTRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions
While yeast Rap1 regulates telomere length and protects telomeres from non-homologous end joining, its role in higher eukaryotes is controversial. Here the authors present evidence that in mammals, RAP1 cooperates with TRF2 to prevent homologous recombination-mediated repair of telomeres.
- Rekha Rai
- , Yong Chen
- & Sandy Chang
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| Open AccessDynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions
DNA-binding proteins need to scan the genome to find their targets though how this occurs in the crowded nuclear environment is poorly understood. Here the authors use single-molecular fluorescence to show the repair complex Msh2-Msh3 can hop over blocks that impede the sliding complex Msh2-Msh6.
- Maxwell W. Brown
- , Yoori Kim
- & Ilya J. Finkelstein
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| Open AccessProbing the target search of DNA-binding proteins in mammalian cells using TetR as model searcher
During transcription, replication and repair, DNA-binding proteins must find specific interaction sites hidden within a vast excess of genomic DNA. Here the authors use single-molecule tracking to quantitatively determine the contributions of the different processes that underlie target search in human cells.
- Davide Normanno
- , Lydia Boudarène
- & Maxime Dahan
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| Open AccessDirect observation of TALE protein dynamics reveals a two-state search mechanism
TALEs are programmable DNA-binding proteins with practical use in genome engineering and synthetic biology. Here the authors use single-molecule fluorescence microscopy to establish that TALE proteins function using two distinct DNA-interaction modes during sequence-specific target search.
- Luke Cuculis
- , Zhanar Abil
- & Charles M. Schroeder
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Article
| Open AccessReal-time submillisecond single-molecule FRET dynamics of freely diffusing molecules with liposome tethering
Single-molecule fluorescence resonance energy transfer is widely used to probe biomolecular dynamics, but is limited by its temporal resolution. Here, Kim et al. push the limit to submillisecond for the duration of tens of milliseconds by tethering target molecules to liposomes in buffer solutions.
- Jae-Yeol Kim
- , Cheolhee Kim
- & Nam Ki Lee
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Article
| Open AccessHsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70 between modules
The chaperones Hsp70 and Hsp90 are physically linked via the cochaperone Sti1/Hop, that has two binding sites for Hsp70. Here, Röhl et al.show that binding of Hsp90 changes the conformation of Sti1/Hop and determines to which site Hsp70 binds, perhaps facilitating transfer of client proteins from Hsp70 to Hsp90.
- Alina Röhl
- , Daniela Wengler
- & Johannes Buchner
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The cleavage pattern of TDP-43 determines its rate of clearance and cytotoxicity
TAR DNA-binding protein of 43 kDa (TDP-43) and its C-terminal fragment of 25 kDa (CTF25) play critical roles in several neurodegenerative diseases but the cleavage site that generates CTF25 remains undetermined. Here the authors show that caspase-4 cleaves TDP-43 after Aps174 generating CTF25, and this leads to TDP-43 clearance and increased cell viability.
- Quan Li
- , Moe Yokoshi
- & Yukio Kawahara
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Article
| Open AccessCytoplasmic TAF2–TAF8–TAF10 complex provides evidence for nuclear holo–TFIID assembly from preformed submodules
TFIID is an essential transcription factor complex that controls the expression of most protein-coding genes in eukaryotes. Here the authors identify and characterize a complex containing TAF2, TAF8 and TAF10, which assembles in the cytoplasm before integration into the nuclear holo–TFIID complex.
- Simon Trowitzsch
- , Cristina Viola
- & Imre Berger
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| Open AccessCpG island-mediated global gene regulatory modes in mouse embryonic stem cells
CpG islands are high GC content DNA elements that surround the majority of transcriptional start sites in eukaryotes. Here, the authors analyse over 200 genomic data sets to provide new insight into global CpG islands-dependent regulatory mechanisms in differentiated and pluripotent stem cells.
- Samuel Beck
- , Bum-Kyu Lee
- & Jonghwan Kim
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Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions
Several recent studies suggest that telomerase has key physiologic functions beyond its well-known role telomere maintenance. Here, Garcia Gonzalez et al. implicate telomerase in the regulation of ribosomal DNA transcription by RNA polymerase I.
- Omar Garcia Gonzalez
- , Robin Assfalg
- & Sebastian Iben
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Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides
The expression of specific genes can be controlled by the combination of DNA-binding proteins, which determines their binding site selectivity. Here, simplified synthetic basic region leucine zipper-based peptides are induced to dimerize either through their C- or N-terminus, and thus are targeted to different DNA sequences.
- Jesús Mosquera
- , Adrián Jiménez-Balsa
- & José L Mascareñas
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Article
| Open AccessAlba shapes the archaeal genome using a delicate balance of bridging and stiffening the DNA
How the genome is physically organized is less understood in archaea than in eubacteria or eukaryotes. Laurens et al. measure DNA binding by the Sulfolobus solfataricusproteins Alba1 and Alba2 using single-molecule techniques and conclude that the presence of Alba2 leads to more bridging between DNA.
- Niels Laurens
- , Rosalie P.C. Driessen
- & Gijs J.L. Wuite
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Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains
The peptide sequence of transcription activator-like effectors (TALEs) can be customized to tailor the binding of TALEs to specific DNA sequences. Conget al. improve TALE specificity for guanine binding and use a genetic construct based on TALEs to efficiently repress expression of a target gene.
- Le Cong
- , Ruhong Zhou
- & Feng Zhang
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Article
| Open AccessThe structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
CXXC domain proteins bind to CpG DNA sequences and influence chromatin modification. Xuet al.report crystal structures of the CXXC protein CFP1, a component of the SETD1 histone H3K4 methyl transferase complex, and study the molecular mechanisms of DNA-binding specificity.
- Chao Xu
- , Chuanbing Bian
- & Jinrong Min