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 structure and the Werner protein modulate human DNA polymerase delta-dependent replication dynamics within the common fragile site FRA16D
TL;DR: The data support a model whereby CFS expression during cellular stress is due to a combination of factors—density of specific DNA secondary-structures within a genomic region and asymmetric rates of strand synthesis.
Journal ArticleDOI
PTEN regulates RPA1 and protects DNA replication forks
Guangxi Wang,Yang Li,Pan Wang,Hui Liang,Ming Cui,Minglu Zhu,Limei Guo,Qian Su,Yujie Sun,Michael A. McNutt,Yuxin Yin +10 more
TL;DR: It is shown that deletion of PTEN leads to replication fork collapse and chromosomal instability upon fork stalling following nucleotide depletion induced by hydroxyurea, and proposed that RPA1 is a target ofPTEN function in fork protection and that PTEN maintains genome stability through regulation of DNA replication.
Journal ArticleDOI
Recombination and Replication
TL;DR: This review focuses on the roles that recombination enzymes play in underpinning genome duplication, aiding replication fork movement in the face of the many replisome barriers that challenge genome stability.
Journal ArticleDOI
The DNA damage response in mammalian oocytes
TL;DR: The different aspects of the response to DNA damage in mammalian oocytes are reviewed, including the oocyte DNA damage response from embryonic life to adulthood and throughout oocyte development.
Journal ArticleDOI
R‐loops cause replication impairment and genome instability during meiosis
TL;DR: It is concluded that R‐loops can form during meiosis causing replication impairment with deleterious results and RNase H partially suppressed the replication impairment and the DNA‐damage accumulation.
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.