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
DNA end resection--unraveling the tail.
TL;DR: Recent in vitro and in vivo findings that shed more light into the mechanisms of DSB processing in mitotic and meiotic DSB repair as well as in telomere metabolism are reviewed.
Journal ArticleDOI
Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange
Sarah Lambert,Ken-ichi Mizuno,Joël Blaisonneau,Sylvain Martineau,Roland Chanet,Karine Fréon,Johanne M. Murray,Antony M. Carr,Giuseppe Baldacci +8 more
TL;DR: It is demonstrated that template exchange occurs during recombination-dependent fork restart at the expense of genome rearrangements, and that the Srs2 helicase promotes both fork restart and template exchange.
Journal ArticleDOI
The INO80 chromatin remodeling complex in transcription, replication and repair.
TL;DR: The Ino80 ATPase is a member of the SNF2 family of ATPases and functions as an integral component of a multisubunit ATP-dependent chromatin remodeling complex, which contributes to a wide variety of chromatin-dependent nuclear transactions, including transcription, DNA repair and DNA replication.
Journal ArticleDOI
Co-orientation of replication and transcription preserves genome integrity.
TL;DR: It is strongly suggested that preservation of genome integrity drives the evolution of co-orientation of replication and transcription, a conserved feature of genome organization.
Journal ArticleDOI
Human DHX9 helicase preferentially unwinds RNA-containing displacement loops (R-loops) and G-quadruplexes.
TL;DR: Human DHX9 helicase, also known as nuclear DNA helicase II (NDH II) and RNA helicase A (RHA), belongs to the SF2 superfamily of nucleic acid unwinding enzymes and preferably unwound R-loops and DNA-based G-quadruplexes indicating that these structures may be biologically relevant.
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.