Journal ArticleDOI
Genome instability: a mechanistic view of its causes and consequences
TLDR
The causes and consequences of instability are reviewed with the aim of providing a mechanistic perspective on the origin of genomic instability.Abstract:
Genomic instability in the form of mutations and chromosome rearrangements is usually associated with pathological disorders, and yet it is also crucial for evolution. Two types of elements have a key role in instability leading to rearrangements: those that act in trans to prevent instability--among them are replication, repair and S-phase checkpoint factors--and those that act in cis--chromosomal hotspots of instability such as fragile sites and highly transcribed DNA sequences. Taking these elements as a guide, we review the causes and consequences of instability with the aim of providing a mechanistic perspective on the origin of genomic instability.read more
Citations
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Journal ArticleDOI
Nuclear Receptor-Induced Chromosomal Proximity and DNA Breaks Underlie Specific Translocations in Cancer
Chunru Lin,Liuqing Yang,Bogdan Tanasa,Bogdan Tanasa,Kasey R. Hutt,Bong-Gun Ju,Bong-Gun Ju,Kenneth A. Ohgi,Jie Zhang,David W. Rose,Xiang-Dong Fu,Christopher K. Glass,Michael G. Rosenfeld +12 more
TL;DR: The data suggest that the confluence of two parallel pathways initiated by liganded nuclear receptor and genotoxic stress underlies nonrandom tumor translocations, which may function in many types of tumors and pathological processes.
Journal ArticleDOI
Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements
Michael C. Haffner,Martin J. Aryee,Antoun Toubaji,David M. Esopi,Roula Albadine,Bora Gurel,William B. Isaacs,G. Steven Bova,Wennuan Liu,Jianfeng Xu,Alan K. Meeker,George J. Netto,Angelo M. De Marzo,William G. Nelson,Srinivasan Yegnasubramanian +14 more
TL;DR: It is shown that androgen signaling promotes co-recruitment of androgen receptor and topoisomerase II beta (TOP2B) to sites of TMPRSS2-ERG genomic breakpoints, triggering recombinogenic TOP2B-mediated DSBs.
Journal ArticleDOI
A Genome-wide siRNA Screen Reveals Diverse Cellular Processes and Pathways that Mediate Genome Stability
Renee D. Paulsen,Deena V. Soni,Roy Wollman,Angela T. Hahn,Muh-Ching Yee,Anna Guan,Jayne Hesley,Steven C. Miller,Evan F. Cromwell,David E. Solow-Cordero,Tobias Meyer,Karlene A. Cimprich +11 more
TL;DR: A genome-wide siRNA screen was employed to identify additional genes involved in genome stabilization by monitoring phosphorylation of the histone variant H2AX, and data indicate that preservation of genome stability is mediated by a larger network of biological processes than previously appreciated.
Journal ArticleDOI
Collisions between Replication and Transcription Complexes Cause Common Fragile Site Instability at the Longest Human Genes
TL;DR: The results show that, on the longest human genes, collisions of the transcription machinery with a replication fork are inevitable, creating R-loops and consequent CFS formation, and functional replication machinery needs to be involved in the resolution of conflicts between transcription and replication machineries to ensure genomic stability.
Journal ArticleDOI
Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription
Sandie Tuduri,Sandie Tuduri,Laure Crabbe,Chiara Conti,Hélène Tourrière,Heidi Holtgreve-Grez,Anna Jauch,Véronique Pantesco,John De Vos,Aubin Thomas,Charles Theillet,Yves Pommier,Jamal Tazi,Arnaud Coquelle,Philippe Pasero +14 more
TL;DR: Data indicate that Top1 prevents replication fork collapse by suppressing the formation of R-loops in an ASF/SF2-dependent manner, and proposes that interference between replication and transcription represents a major source of spontaneous replication stress, which could drive genomic instability during the early stages of tumorigenesis.
References
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Book
DNA Repair and Mutagenesis
TL;DR: Nucleotide excision repair in mammalian cells: genes and proteins Mismatch repair The SOS response and recombinational repair in prokaryotes Mutagenesis in proKaryote Mutagenisation in eukaryotes Other DNA damage tolerance responses in eUKaryotes.
Journal ArticleDOI
Instability and decay of the primary structure of DNA
TL;DR: The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils.
Journal ArticleDOI
DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139
TL;DR: In this paper, a histone H2AX species that has been phosphorylated specifically at serine 139 was found to be a major component of DNA double-stranded break.
Journal ArticleDOI
ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks
TL;DR: The results clearly establish ATM as the major kinase involved in the phosphorylation of H2AX and suggest that ATM is one of the earliest kinases to be activated in the cellular response to double-strand breaks.
Journal ArticleDOI
Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
Vassilis G. Gorgoulis,Leandros-Vassilios F. Vassiliou,Panagiotis Karakaidos,Panayotis Zacharatos,Athanassios Kotsinas,Triantafillos Liloglou,Monica Venere,Richard A. DiTullio,Nikolaos G. Kastrinakis,Brynn Levy,Dimitris Kletsas,Akihiro Yoneta,Meenhard Herlyn,Christos Kittas,Thanos D. Halazonetis,Thanos D. Halazonetis +15 more
TL;DR: A panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis as discussed by the authors.