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
Overexpression and Mislocalization of the Chromosomal Segregation Protein Separase in Multiple Human Cancers
Rene Meyer,Viacheslav Y. Fofanov,Anil K. Panigrahi,Fatima A. Merchant,Nenggang Zhang,Debananda Pati +5 more
TL;DR: The results of this study further strengthen the hypothesis that Separase might be an oncogene, whose overexpression induces tumorigenesis, and indicates thatSeparase overeexpression and aberrant nuclear localization are common in many tumor types and may predict outcome in some human cancers.
Journal ArticleDOI
An N-terminal acidic region of Sgs1 interacts with Rpa70 and recruits Rad53 kinase to stalled forks.
Anna Maria Hegnauer,Anna Maria Hegnauer,Nicole Hustedt,Nicole Hustedt,Kenji Shimada,Brietta L. Pike,Markus Vogel,Philipp Amsler,Philipp Amsler,Seth M. Rubin,Fred van Leeuwen,Aude Guénolé,Haico van Attikum,Nicolas H. Thomä,Susan M. Gasser,Susan M. Gasser +15 more
TL;DR: It is proposed that the recruitment of Rad53 by phosphorylated Sgs1 promotes the replication checkpoint response on HU, which increases lethality selectively in cells lacking Mus81, Slx4, SlX5 or Slx8.
Journal ArticleDOI
Histone H3K56 Acetylation, Rad52, and Non-DNA Repair Factors Control Double-Strand Break Repair Choice with the Sister Chromatid
TL;DR: This work demonstrates the existence of specific functions to guarantee SCR as the main repair event for replication-born DSBs that can occur by two pathways, one Rad51-dependent and the other Pol32-dependent.
Journal ArticleDOI
RecA-Dependent DNA Repair Results in Increased Heteroplasmy of the Arabidopsis Mitochondrial Genome
Marie Miller-Messmer,Kristina Kühn,Marc Bichara,Monique Le Ret,Patrice Imbault,José M. Gualberto +5 more
TL;DR: Functional analyses of the two Arabidopsis mitochondrial RecAs revealed that RECA3 is required for different recombination-dependent repair pathways that significantly contribute to plant fitness under stress, and it was shown that these are transmitted to the plant progeny, enhancing the potential for mitochondrial genome evolution.
Journal ArticleDOI
The FHIT gene product: tumor suppressor and genome “caretaker”
TL;DR: Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.
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.