Nuclear architecture, chromosome domains and genetic damage

Folle, Gustavo A.

doi:10.1016/j.mrrev.2007.08.005

Cited by 42 publications

(27 citation statements)

References 62 publications

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“…The G-banding pattern suggests the existence of Alu I restriction sites in both Xp e and Xq h , since Alu I recognizes the 5 -AG f CT-3 target inside SINE (Alu) elements which reside within the constitutive hamster sub-genome (Giemsa-light bands) [Bryant, 1984[Bryant, , 2007Kessler, 1987 Several approaches support these assumptions. Folle andObe [1995, 1996] and Folle et al [1997Folle et al [ , 1998] reported that BP induced by Alu I, Bam HI and DNAse I in CHO cells predominate in euchromatic Xp e . Additionally, heterochromatic Xq h was resistant to direct digestion with these endonucleases in metaphase spreads [Folle et al, 1997].…”

Section: Role Of Asynchronously Replicating Eu/heterochromatic Regionmentioning

confidence: 99%

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Asynchronously Replicating Eu/Heterochromatic Regions Shape Chromosome Damage

Tomaso

Martínez‐López²,

Palitti³

2010

Cytogenet Genome Res

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In order to shed more light on the influence of DNA replication on the formation and distribution of chromosome aberrations, breakpoints (BP) produced by UV-C and AluI were assigned either to the early replicating short euchromatic arm (Xp_e) or to the late replicating long heterochromatic arm (Xq_h) of the Chinese hamster (CHO9) X chromosome. Early (ES) or late (LS) S-phase cells were assessed by pulse incorporating the base analogue 5-bromo-2′-deoxyuridine (BrdU) immediately after UV-C irradiation (30 J/m²) or AluI (20 U) poration followed by BrdU immunodetection with FITC-tagged antibodies in metaphase spreads. Short (30 s) UV-C exposures (1 J/m²/s) induced BP preferentially in Xq_h in LS cells and a random distribution of BP along Xp_e and Xq_h in ES cells. However, BP induced by long (5 min) UV-C exposures (0.1 J/m²/s) clustered according to arm replication time (Xp_e during ES and Xq_h along LS). Giemsa-stained metaphases showed elevated frequencies of UV-C induced chromatid-type aberrations and gaps, especially in cells exposed to longer UV-C irradiation. BP induced by AluI clustered in Xp_e in ES but distributed randomly during LS. In contrast to UV-C, AluI did not produce an increase in the yield of gaps, neither in ES nor in LS cells. Putative mechanisms underlying the observed distributions of chromosome damage in replicating CHO9 cells exposed to UV-C and AluI are discussed.

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Section: Role Of Asynchronously Replicating Eu/heterochromatic Regionmentioning

confidence: 99%

“…Furthermore, the transcriptional and organizational status of chromatin (euchromatin or heterochromatin) in addition to chromatin modifications during the cell cycle may also play a role in the production of CA [Folle et al, 1998;Martínez-López et al, 2001, 2007Martínez-López and Di Tomaso, 2006;Di Tomaso et al, 2008;Folle, 2008].…”

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confidence: 99%

Asynchronously Replicating Eu/Heterochromatic Regions Shape Chromosome Damage

Tomaso

Martínez‐López²,

Palitti³

2010

Cytogenet Genome Res

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“…Therefore, clustering of H4 +a chromatin, RIDGEs, radiation BP clusters and deregulated genes might be at least partially explained on the basis of a nuclear compartment-biased response to DNA damage determined by an enhanced sensitivity of highly expressed genomic regions. In this respect, spatial positioning, proximity and intermingling of specific chromosome segments may also be crucial in the pathway to cell transformation [Folle, 2008]. Clustering of recurrent CA in tumors, radiation and evolutionary BP, IS and deregulated genes in specific human chromosome regions could be due to topological, dynamical and even compositional constraints [Pevzner and Tesler, 2003;Sabbia et al, 2009] that favor their intranuclear vicinity.…”

Section: Discussionmentioning

confidence: 99%

Close Encounters: RIDGEs, Hyperacetylated Chromatin, Radiation Breakpoints and Genes Differentially Expressed in Tumors Cluster at Specific Human Chromosome Regions

Folle

Liddle

Lafon-Hughes

et al. 2010

Cytogenet Genome Res

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Through analysis of published data we positioned along human chromosome idiograms (850 bands) hyperacetylated H4 chromatin (H4^+a), regions of increased gene expression (RIDGEs), antiRIDGEs, ionizing radiation breakpoints, integration sites of highly expressed GFP reporter constructs and candidate genes differentially expressed in tumor tissues. Highly expressed regions of the human genome (especially RIDGEs) seem to be more sensitive to radiation damage. Comparatively, antiRIDGEs appear as radiation resistant. Tumor deregulated genes tend to cluster along and in the neighborhood of RIDGEs. We detected 35 clusters of genes differentially expressed in tumor tissues which colocalize with RIDGEs; 23 of these clusters also exhibit radiation damage. RIDGEs also accumulate highly expressed GFP reporter construct integration sites, evolutionary breakpoints as well as amplicons and/or deletion-prone chromosome segments in tumors. This could indicate that abnormal gene (up- or down-) regulation might require high-throughput transcription nuclear micro-environments to occur. Our results suggest that the human genome is a combination of regions with marked disparities regarding the topology of increased gene expression, ionizing radiation damage, evolutionary breakpoints, integration sites, and abnormal gene regulation.

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“…Therefore, the different sensitivity of chromatin states to damaging agents could explain the difference in γH2AX signaling between 1-Z1 and 1-Z6. In this respect, it was reported that regions with dissimilar chromatin organization may exhibit distinct sensibilities to chemical clastogens [47] [62].…”

Section: Chromosome Regionsmentioning

confidence: 99%