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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.

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Citations
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Journal ArticleDOI

Correction: The Caenorhabditis elegans THO Complex Is Required for the Mitotic Cell Cycle and Development

TL;DR: This research presents a novel probabilistic procedure that allows for direct measurement of the response of the immune system to earthquake-triggered landsliding.
Dissertation

Efficient support of DNA replication functions by DNA ligase 3 in vertebrate cells

TL;DR: The results show a remarkable and hitherto unexpected functional flexibility in DNA replication of LIG1 and LIG3 in vertebrates and conclusively show that the ZnFn domain of Ligs3 is essential for the DNA replication function of Lig3, although it is not essential for maintaining mitochondrial integrity.
Book ChapterDOI

Poly(ADP) Ribose Polymerase at the Interface of DNA Damage Signaling and DNA Repair

TL;DR: Two major pathways which have evolved to repair DNA DSBs are focused on: nonhomologous end joining (NHEJ) and homologous recombination (HR).
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

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.
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