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| Open AccessChromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability
Topoisomerase 1 (TOP1) relieves superhelical tension when DNA strands are unwound during transcription. Here, Husain et al. report that SMARCA4, an ATP-dependent chromatin remodeller, is associated with TOP1 and suppresses transcription-associated genomic instability.
- Afzal Husain
- , Nasim A. Begum
- & Tasuku Honjo
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| Open AccessLimiting replication stress during somatic cell reprogramming reduces genomic instability in induced pluripotent stem cells
The expression of reprogramming factors can induce replication stress in induced pluripotent stem cells. In this study, to reduce such genomic instability, Ruiz et al.increase CHK1 kinase levels and nucleoside supplementation during reprogramming.
- Sergio Ruiz
- , Andres J. Lopez-Contreras
- & Oscar Fernandez-Capetillo
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| Open AccessmRIN for direct assessment of genome-wide and gene-specific mRNA integrity from large-scale RNA-sequencing data
With the rapid increase in the volume of publically available RNA-seq data, quality control is an increasingly important consideration. Here Feng et al. develop mRIN, a method to directly assess mRNA integrity, and show that RNA degradation in post-mortem samples has a strong impact on global expression profiles.
- Huijuan Feng
- , Xuegong Zhang
- & Chaolin Zhang
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Article
| Open AccessHaploinsufficiency for BRCA1 leads to cell-type-specific genomic instability and premature senescence
BRCA1 functions in all cell types to help preserve genomic stability but oncogenesis is restricted to only a few tissues. Here Sedic et al. demonstrate a novel BRCA1haploinsufficiency-induced senescence pathway in epithelial cells.
- Maja Sedic
- , Adam Skibinski
- & Charlotte Kuperwasser
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Oncogenes create a unique landscape of fragile sites
Aberrant oncogene expression can cause replication stress leading to chromosomal breaks. Here the authors map the chromosomal break loci induced by two different oncogenes and by a replication inhibitor, and show that each treatment induces a unique pattern of breaks in the same cell type.
- Karin Miron
- , Tamar Golan-Lev
- & Batsheva Kerem
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RECQ5-dependent SUMOylation of DNA topoisomerase I prevents transcription-associated genome instability
DNA topoisomerase I (TOP1) maintains DNA topology by relaxing supercoiled DNA during transcription. Here, the authors show that SUMOylation of TOP1 is necessary for its association with transcriptionally active RNA polymerase II and can reduce R-loops, preventing TOP1-induced DNA damage.
- Min Li
- , Subhash Pokharel
- & Yilun Liu
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Article
| Open AccessSpartan deficiency causes genomic instability and progeroid phenotypes
Spartan/DVC1 is a translesion synthesis regulator with important roles in cellular DNA damage tolerance. Here, the authors report that Spartan is essential for DNA lesion bypass and that Spartan insufficiency in mice causes chromosomal instability, cellular senescence and early onset of age-related phenotypes.
- Reeja S. Maskey
- , Myoung Shin Kim
- & Yuichi J. Machida
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Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity
Nucleotide excision repair protects the genome from UV light-induced damage. Here, Puumalainen et al. show that chromatin retention of the UV lesion sensors DDB2 and XPC due to a lack of p97 segregase impairs excision repair, revealing that DNA lesion-associated protein homeostasis affects genome stability.
- Marjo-Riitta Puumalainen
- , Davor Lessel
- & Hanspeter Naegeli
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A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites
Genomes contain tracts of tandem guanines, which can adopt stable G-quadruplex structures that obstruct replication fork movement. Here, Koole et al. describe a non-canonical polymerase Theta-dependent repair pathway that prevents genomic instability caused by these replication barriers.
- Wouter Koole
- , Robin van Schendel
- & Marcel Tijsterman
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| Open AccessR-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli
DNA double-strand breaks commonly occur in all replicating cells. Wimberly and colleagues show that in non-replicating cells, aborted transcription/translation forms RNA/DNA hybrid R-loops that prime origin-independent replication, leading to DNA breakage, point mutations and chromosomal rearrangements.
- Hallie Wimberly
- , Chandan Shee
- & P. J. Hastings
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The RB family is required for the self-renewal and survival of human embryonic stem cells
While human embryonic stem cells (ESC) hold great therapeutic promise, many aspects of their basic biology remain poorly understood. Conklin et al.show that too much or too little activation of RB family proteins is detrimental to human ESC populations and identify unique cell cycle regulatory networks in these cells.
- Jamie F. Conklin
- , Julie Baker
- & Julien Sage
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Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome
Mutations in the DNA helicaseBLM cause Bloom syndrome, which is characterized by slow replication fork progression and genetic instability. Here, cells lacking BLMare shown to have a defect in cytidine deaminase, which alters the pyrimidine pool and results in replication fork progression with altered velocity.
- Pauline Chabosseau
- , Géraldine Buhagiar-Labarchède
- & Mounira Amor-Guéret