Chromatin modulation and the DNA damage response

Costelloe, Thomas; Fitzgerald, Jennifer; Murphy, Niall; Flaus, Andrew; Lowndes, Noel F.

doi:10.1016/j.yexcr.2006.06.031

Cited by 37 publications

(31 citation statements)

References 85 publications

(129 reference statements)

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“…TDP1 was first identified by mass spectrometry following coimmunoprecipitation of hyperacetylated histone H4 (AcH4) from sonication resistant spermatid extracts (unpublished results) and later by immunofluorescence and immunoblots. The association of a repair enzyme such as TDP1 with AcH4 is consistent with the known requirement of histone hyperacetylation at sites of damage [Costelloe et al 2006]. …”

Section: Endogenous Dna Fragmentation and Repair As Part Of Normal Spsupporting

confidence: 77%

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Leduc¹,

Nkoma²,

Boissonneault³

2008

Systems Biology in Reproductive Medicine

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This paper reviews the possible origin of sperm DNA fragmentation and focuses on the nuclear events associated with spermiogenesis as a potential source of genetic instability and reduced fertilizing potential of the mature male gamete. Recent findings suggest a programmed DNA fragmentation and DNA damage response during the chromatin remodeling steps in spermatids. We also discuss the spermatid DNA repair mechanisms and the possible involvement of condensing proteins, such as transition proteins and protamines, in the process, as this DNA fragmentation is normally not found in late spermatids. We propose that alterations in the chromatin remodeling steps or DNA repair in elongating spermatids may lead to persistent DNA breaks. This vulnerable step of spermiogenesis may provide a clue to the etiology of sperm DNA fragmentation associated with infertility in humans. This vulnerability is further emphasized given the haploid character of spermatids that must resolve programmed double-stranded breaks by an error-prone DNA repair mechanism. Therefore, spermiogenesis has probably been overlooked as an important source of genetic instability.

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Section: Endogenous Dna Fragmentation and Repair As Part Of Normal Spsupporting

confidence: 77%

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Leduc¹,

Nkoma²,

Boissonneault³

2008

Systems Biology in Reproductive Medicine

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“…[50][51][52] It is followed be an increase in the acetylation of H3 at K9, K14, K18, K23 and K27 and of H4 at K5, K8, K12 and K16. 53,54 Acetylation of lysine residues neutralizes the positive charges on histones and reduces the affinity between histones and DNA, a plausible route to relaxation of the normally tight chromatin structure. Thus, these changes are expected to facilitate the access of different DNA repair proteins to the sites of damage.…”

Section: Chromatin Alterations In the Dna Damage Responsementioning

confidence: 99%

“…Thus, these changes are expected to facilitate the access of different DNA repair proteins to the sites of damage. 54 Indeed, the recruitment of DNA repair factors to ionizing radiation-induced foci is impaired in H2AX null cells. 55 Consequently, these cells are chromosomally unstable and show an increased susceptibility to cancer.…”

Section: Chromatin Alterations In the Dna Damage Responsementioning

confidence: 99%

Paving the way for H2AX phosphorylation: Chromatin changes in the DNA damage response

Ayoub

Jeyasekharan²,

Bernal³

et al. 2009

Cell Cycle

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“…It is also now apparent that multiple ATP-dependent chromatin remodelling complexes contribute to cellular survival after DNA damage and play a role directly at the sites of DNA damage. These events have been extensively reviewed elsewhere (Peterson and Cote, 2004;Foster and Downs, 2005;Morrison and Shen, 2005;van Attikum and Gasser, 2005;Costelloe et al, 2006;Downs et al, 2007). Moreover, the contribution of chromatin modifying complexes and enzymes to tumourigenesis was the subject of a recent issue of Oncogene reviews (volume 26, issue 37).…”

Section: Chromatin and The Dna Damage Responsementioning

confidence: 99%

Chromatin structure and DNA double-strand break responses in cancer progression and therapy

Downs

2007

Oncogene

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Defects in the detection and repair of DNA double-strand breaks (DSBs) have been causatively linked to tumourigenesis. Moreover, inhibition of DNA damage responses (DDR) can increase the efficacy of cancer therapies that rely on generation of damaged DNA. DDR must occur within the context of chromatin, and there have been significant advances in recent years in understanding how the modulation and manipulation of chromatin contribute to this activity. One particular covalent modification of a histone variant-the phosphorylation of H2AX-has been investigated in great detail and has been shown to have important roles in DNA DSB responses and in preventing tumourigenesis. These studies are reviewed here in the context of their relevance to cancer therapy and diagnostics. In addition, there is emerging evidence for contributions by proteins involved in mediating higher order structure to DNA DSB responses. The contributions of a subset of these proteins-linker histones and high-mobility group box (HMGB) proteins-to DDR and their potential significance in tumourigenesis are discussed.

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Chromatin modulation and the DNA damage response

Cited by 37 publications

References 85 publications

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Paving the way for H2AX phosphorylation: Chromatin changes in the DNA damage response

Chromatin structure and DNA double-strand break responses in cancer progression and therapy

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