Links between chromatin structure, DNA repair and chromosome fragility

Surrallés, Jordi; Puerto, S.; Ramírez, María-José; Creus, A.; Marcos, Ricard; Mullenders, Leon H.F.; Natarajan, A.T.

doi:10.1016/s0027-5107(98)00093-1

Cited by 33 publications

(15 citation statements)

References 29 publications

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“…Differences in chromatin organization have been implicated in the sensitivity of cells to ionizing radiation [18,21]. Cell lines are more sensitive to radiationinduced double-stranded DNA breaks when histone proteins are removed by high salt concentration [22].…”

Section: Discussionmentioning

confidence: 99%

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

et al. 2005

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Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase. Am.

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Section: Discussionmentioning

confidence: 99%

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

et al. 2005

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“…The CA can be induced by chemical and physical agents, or may arise during the process of DNA repair, and this is highly infl uenced by the chromatin structure and the transcriptional activity [ 4 ]. According to Palitti [ 5 ], the induction of damage in DNA and its processing by repair enzymes are affected by different levels of chromatin organization.…”

Section: Origin Of Chromosomal Aberrations: Uses In Vitro and In Vivomentioning

confidence: 99%

Chromosomal Aberration Test Utilities In Vitro and In Vivo

Guimarães

Alcântara

et al. 2014

Genotoxicity and DNA Repair

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Human populations are frequently exposed to several mutagenic agents that have the potential to damage the DNA, and this, in many cases, may result in the formation of chromosomal aberrations (CAs). CAs are recognized as an important biomarker of human exposure, being a very important tool for environmental biomonitoring. Although there are several types, little is known about the mechanisms involved in the processing of induced lesions in DNA and how these could result in CAs. Thus, cytogenetics and molecular cytogenetics are tools of great importance for identifying these agents, the conditions that can exercise their mutagenic potential, and their action mechanism. This chapter discusses the history of CA formation and some cytogenetic protocols that may be used to perform the chromosomal aberration test in in vivo and in vitro studies.

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“…Any other chromosomal rearrangement that does not fulfil this essential criterion for survival in an expanded clone of cells will never become visible and will disappear during natural cell wastage. Conversely, it has been suggested that the consistent involvement of specific and apparently non-random regions of the genome in reciprocal translocations results from chromatin at particular loci being especially susceptible to DNA damage [11]. …”

Section: The T(9;22) Reciprocal Chromosomal Translocationmentioning

confidence: 99%

Cytogenetic and Molecular Genetic Aspects of Chronic Myeloid Leukaemia

Barnes¹,

Melo²

2002

Acta Haematol

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Chronic myeloid leukaemia (CML) is caused by the product of the BCR-ABL oncogene, located on the Philadelphia (Ph) chromosome. BCR-ABL is generated as a result of a reciprocal t(9;22) chromosomal translocation. The mechanisms responsible for this illegitimate recombination event remain elusive but are presumed to require a close spatial association of the translocation partners (chromosomes 9 and 22). BCR-ABL fusion transcripts can be detected by a sensitive reverse transcription-polymerase chain reaction (RT-PCR) in the leucocytes of some healthy individuals suggesting that chromosomal translocations may occur frequently in the general population. The presence of BCR-ABL fusion transcripts does not imply that the individual will inevitably develop CML since other conditions must be favourable for expansion of the abnormal clone. Breakpoints in the ABL gene occur within a 5′ segment. BCR-ABL fusion transcripts lack ABL exon a1 and consist of BCR exons fused directly to ABL exon a2. The breakpoints in the BCR gene on chromosome 22 are found within three defined regions. Depending on the position of the BCR breakpoint, fusion genes are generated that encode 190-, 210- or 230-kD forms of the Bcr-Abl tyrosine kinase. Since the ABL component of the fusion gene is largely invariant, it follows that variability in disease phenotype may be due to protein sequences encoded by the translocation partner, BCR. Different disease phenotypes are associated with each of the three Bcr-Abl oncoproteins, p190^Bcr-Abl, p210^Bcr-Abland p230^Bcr-Abl. Mechanisms associated with malignant transformation include altered cellular adhesion, activation of mitogenic signalling pathways, inhibition of apoptosis and proteasomal degradation of physiologically important cellular proteins. CML is subject to an inexorable progression from an ‘indolent’ chronic phase to a terminal blast crisis. Disease progression is presumed to be associated with the phenomenon of genomic instability.

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Links between chromatin structure, DNA repair and chromosome fragility

Cited by 33 publications

References 29 publications

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

Chromosomal Aberration Test Utilities In Vitro and In Vivo

Cytogenetic and Molecular Genetic Aspects of Chronic Myeloid Leukaemia

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