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
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Tartu ülikool loodus- ja tehnoloogiateaduskond molekulaar- ja rakubioloogia instituut
TL;DR: The appearance of certain mutational hot spots is strongly affected by the chromosomal location of the mutational target sequence especially in growing bacteria, which implies that regional differences in chromosomal topology may influence transposition of this mobile element.
Dissertation
Regulation of resection by chromatin associated proteins
TL;DR: A new role of RAD 51 paralogs is described, independent of RAD51, in earlier steps of DSB repair than those described helping RAD51 in recombination, which seems to hamper the recruitment of NHEJ machinery to resected DNA to promote the HR pathway.
Journal ArticleDOI
Sir2 and Reb1 antagonistically regulate nucleosome occupancy in subtelomeric X-elements and repress TERRAs by distinct mechanisms
TL;DR: This work shows that sir2 mutant strains display a specific loss of a nucleosome residing in the X-elements and that this deficiency is remarkably consistent between different telomeres, and presents evidence that Reb1 restricts TERRAs by terminating transcription.
Journal ArticleDOI
Advanced Collaborative Emissions Study Auxiliary Findings on 2007-Compliant Diesel Engines: A Comparison With Diesel Exhaust Genotoxicity Effects Prior to 2007
TL;DR: Results indicated that the 2007-compliant diesel engine reduced measurable reactive oxygen species–associated tissue derangements and suggested that the2007 standards–based mitigation approaches were effective.
Mutation and association analyses of the candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A in patients with unexplained MSH2-deficient tumors Nils RahnerFelix F. BrockschmidtVerena SteinkePhilip KahlTim Becker • Hans F. A. VasenJuul T. WijnenCarli J. M. TopsElke Holinski-Feder • Marjolijn J. L. LigtenbergLiesbeth SpruijtHeike GorgensSusanne Stemmler • Matthias KloorWolfgang DietmaierThe Dutch Cancer Genetics Group • Johannes SchumacherMarkus M. NothenPeter Propping
N. Rahner,F. F. Brockschmidt,Verena Steinke,J. Schumacher,P. Propping,P. Kahl,Thomas Becker,H. F. A. Vasen,C. J. M. Tops,M. J. L. Ligtenberg,L. Spruijt,S. Stemmler,M. Kloor,W. Dietmaier +13 more
TL;DR: The present results suggest that neither rare nor common genetic variants in ESR1, ESR2, MAX, PCNA, or KAT2A contribute to the development of Lynch syndrome.
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.