3D genome organization contributes to genome instability at fragile sites.

Nature Communications
Dan SarniBatsheva Kerem

Abstract

Common fragile sites (CFSs) are regions susceptible to replication stress and are hotspots for chromosomal instability in cancer. Several features were suggested to underlie CFS instability, however, these features are prevalent across the genome. Therefore, the molecular mechanisms underlying CFS instability remain unclear. Here, we explore the transcriptional profile and DNA replication timing (RT) under mild replication stress in the context of the 3D genome organization. The results reveal a fragility signature, comprised of a TAD boundary overlapping a highly transcribed large gene with APH-induced RT-delay. This signature enables precise mapping of core fragility regions in known CFSs and identification of novel fragile sites. CFS stability may be compromised by incomplete DNA replication and repair in TAD boundaries core fragility regions leading to genomic instability. The identified fragility signature will allow for a more comprehensive mapping of CFSs and pave the way for investigating mechanisms promoting genomic instability in cancer.

References

Oct 1, 2003·Molecular and Cellular Biology·Eitan ZlotorynskiBatsheva Kerem
Feb 12, 2004·Bioinformatics·M J L de HoonS Miyano
Apr 15, 2005·Nature·Vassilis G GorgoulisThanos D Halazonetis
Nov 15, 2007·Cytogenetic and Genome Research·S McAvoyD I Smith
Mar 8, 2008·Science·Thanos D HalazonetisJiri Bartek
Oct 10, 2008·PLoS Biology·Ichiro HirataniDavid M Gilbert
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Feb 19, 2010·Nature·Graham R BignellMichael R Stratton
Nov 8, 2011·Nature Structural & Molecular Biology·Benoî Le TallecMichelle Debatisse
Jan 26, 2012·PLoS Genetics·Pierre CaronGaëlle Legube
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jul 3, 2013·Nature Cell Biology·Songmin YingIan D Hickson
Aug 27, 2013·Methods : a Companion to Methods in Enzymology·Michelle T PaulsenMats Ljungman
Jul 6, 2014·Genome Research·Yoav LubelskyDavid M MacAlpine
Jan 18, 2015·Experimental Biology and Medicine·Ge Gao, David I Smith
Jan 27, 2015·Annual Review of Pathology·Morgane Macheret, Thanos D Halazonetis
Apr 25, 2015·Nature Reviews. Cancer·Hélène GaillardAndrés Aguilera
May 12, 2015·Nature Communications·Karin MironBatsheva Kerem
Jun 6, 2015·Trends in Cell Biology·Julie Sollier, Karlene A Cimprich
Dec 4, 2015·Nature·Sheroy MinocherhomjiIan D Hickson
Mar 30, 2016·Annual Review of Biochemistry·Hélène Gaillard, Andrés Aguilera
Apr 12, 2016·Current Opinion in Cell Biology·Dan Sarni, Batsheva Kerem
Jun 4, 2016·Molecular Cell·Jesse R DixonBing Ren
Jun 4, 2016·Molecular Cell·Juan Carlos Rivera-Mulia, David M Gilbert
Jul 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Benoit MiottoKevin Struhl
Nov 30, 2016·Genes & Development·Jessica L Alexander, Terry L Orr-Weaver

❮ Previous
Next ❯

Citations

Nov 11, 2020·Epigenetics & Chromatin·Wen-Jun WangJiu-Wei Cui
Dec 15, 2020·Current Opinion in Cell Biology·Aleksandra Lezaja, Matthias Altmeyer
Apr 2, 2021·The FEBS Journal·Xanita Saayman, Fumiko Esashi
May 6, 2021·International Journal of Molecular Sciences·Lina-Marie BriuJean-Charles Cadoret
Nov 18, 2020·Trends in Genetics : TIG·Alex V NestaChristine R Beck
May 25, 2021·Frontiers in Cell and Developmental Biology·William TremblayAnne Fernandez-Vidal
Jun 3, 2021·International Journal of Molecular Sciences·Lilas CourtotValérie Bergoglio
Jun 12, 2021·Royal Society Open Science·Camelia Mocanu, Kok-Lung Chan
Aug 28, 2021·Biomolecules·Commodore St GermainJacqueline H Barlow
Oct 6, 2021·Cell Reports·Capucine Van RechemJohnathan R Whetstine

❮ Previous
Next ❯

Datasets Mentioned

BETA
U13369.1

Methods Mentioned

BETA
Repli-seq
Hi-C
chromosomal aberrations
ChIP-seq
2500 sequencing

Software Mentioned

bowtie2
genomecov
STAR
bedtools shuffle
DESeq2
HiCExplorer
R project for
bedtools2
GENCODE
Cluster

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Genes, Chromosomes & Cancer
Michal Irony-Tur Sinai, Batsheva Kerem
© 2021 Meta ULC. All rights reserved