DNA Damage Leaves its Mark on Chromatin

Polo, Sophie E.; Almouzni, Geneviève

doi:10.4161/cc.6.19.4756

Cited by 13 publications

(11 citation statements)

References 49 publications

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“…Chromatin restoration in the wake of DNA repair involves incorporation of new histones [110,111], and transient recruitment of multiple chromatin modifiers [109]. Occasionally these processes can inflict silencing and thus switch the epigenetic state of a damaged locus [112].…”

Section: Discussionmentioning

confidence: 99%

Replication stress, a source of epigenetic aberrations in cancer?

Jasencakova

Groth

2010

BioEssays

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Cancer cells accumulate widespread local and global chromatin changes and the source of this instability remains a key question. Here we hypothesize that chromatin alterations including unscheduled silencing can arise as a consequence of perturbed histone dynamics in response to replication stress. Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic information thus relies on faithful restoration of chromatin on the new daughter strands. Acute replication stress challenges proper chromatin restoration by deregulating histone H3 lysine 9 mono-methylation on new histones and impairing parental histone recycling. This could facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling. Deregulation of replication in response to oncogenes and other tumor-promoting insults is recognized as a significant source of genome instability in cancer. We propose that replication stress not only presents a threat to genome stability, but also jeopardizes chromatin integrity and increases epigenetic plasticity during tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Replication stress, a source of epigenetic aberrations in cancer?

Jasencakova

Groth

2010

BioEssays

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“…During DDR, they can be included into nucleosomes in the vicinity of DNA-damaged sites by ATP-dependent remodeling complexes. The incorporation of histone variants could participate in the reversion of histone PTMs in order to restore chromatin conformation once DNA repair has finished reinitiating the cell cycle [Polo and Almouzni, 2007].…”

Section: Chromatin Dynamics In Response To Dna Damagementioning

confidence: 99%

Histone Post-Translational Modifications in DNA Damage Response

Méndez-Acuña¹,

Tomaso

Palitti

et al. 2010

Cytogenet Genome Res

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The fact that eukaryotic DNA is packed into chromatin constitutes a physical barrier to enzymes and regulatory factors to reach the DNA molecule for replication, transcription, recombination and repair. Although most studies in this field have concentrated on how chromatin regulates transcription, there is a recent emphasis on studying the role of chromatin in the response to DNA damage. Two main chromatin-remodeling mechanisms have been identified, namely, ATP-dependent chromatin-remodeling complexes and histone post-translational modifications (PTMs). PTMs constitute reversible covalent modifications in aminoacidic residues, such as serine and threonine phosphorylation, lysine acetylation, lysine and arginine methylation and lysine ubiquitylation, among others. Moreover, nucleosome composition can be modified by the incorporation of histone variants, which are assembled into nucleosomes independently of DNA replication. The phosphorylation of the histone variant H2AX (γH2AX) is one of the best examples of histone PTMs in response to DNA damage induction, but many others have recently been revealed. In this review, we focus on and summarize the best-known histone PTMs observed in excision repair (base excision and nucleotide excision) and double-strand break (non-homologous end-joining and homologous recombination) repair pathways. In brief, the interplay between chromatin remodelers and DNA repair factors is discussed in relation to DNA damage response mechanisms.

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“…Significantly, histone modifications have also been identified to be integral to DNA repair processes where they act as signals and landing platforms for various repair proteins [69]. Since aberrant repair is considered a hallmark of cancer, the role of histone modifications and nucleosome displacement in the process is being critically examined [70]. Similarly, hypoxia that sets in growing tumors also mediates a specific gene-expression profile through induction of a typical signature of histone modifications specifically associated with either transcriptional activation or repression that is neither cell type or HIF1-dependent but can mediate a program of tumor cell survival [71].…”

Section: Dysfunctional Histone Modifications and Stem Cells In Ovarian mentioning

confidence: 99%

Modulation Of Gene Expression In Ovarian Cancer By Active And Repressive Histone Marks

Bapat

2010

Epigenomics

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DNA methylation and histone modifications often function concomitantly to drive an aberrant program of gene expression in most cancers. Consequently, they have also been identified as being associated with ovarian cancer. However, several basic issues remain unclear - are these marks established early during normal ovarian functioning, or at a preneoplastic stage, or through a gradual accumulation, or do they arise de novo during transformation? Such issues have been difficult to address in ovarian cancer wherein preneoplastic lesions and progression models have not yet been established and drug-refractive disease progression is rapid and aggressive. The review presents an overview of the known involvement of histone modifications in various cellular states that might contribute to our understanding of epithelial ovarian cancer.

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DNA Damage Leaves its Mark on Chromatin

Cited by 13 publications

References 49 publications

Replication stress, a source of epigenetic aberrations in cancer?

Replication stress, a source of epigenetic aberrations in cancer?

Histone Post-Translational Modifications in DNA Damage Response

Modulation Of Gene Expression In Ovarian Cancer By Active And Repressive Histone Marks

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