With the assumption that a portion that comprises some 10 percent of the genomes in higher organisms cannot be without a raison d'etre, an extensive review led us to conclude that a certain amount of constitutive heterochromatin is essential in multicellular organisms at two levels of organization, chromosomal and nuclear. At the chromosomal level, constitutive heterochromatin is present around vital areas within the chromosomes. Around the centromeres, for example, heterochromatin is believed to confer protection and strength to the centromeric chromatin. Around secondary constrictions, heterochromatic blocks may ensure against evolutionary change of ribosomal cistrons by decreasing the frequency of crossing-over in these cistrons in meiosis and absorbing the effects of mutagenic agents. During meiosis heterochromatin may aid in the initial alignment of chromosomes prior to synapsis and may facilitate speciation by allowing chromosomal rearrangement and providing, through the species specificity of its DNA, barriers against cross-fertilization. At the nuclear level of organization, constitutive heterochromatin may help maintain the proper spatial relationships necessary for the efficient operation of the cell through the stages of mitosis and meiosis. In the unicellular procaryotes, the presence of a small amount of genetic information in one chromosome obviates the need for constitutive heterochromatin and a nuclear membrane. At higher levels of organization, with an increase in the size of the genome and with evolution of cellular and sexual differentiation, the need for compartmentalization and structural components in the nucleus became imminent. The portion of the genome that was concerned with synthesis of ribosomal RNA was enlarged and localized in specific chromosomes, and the centromere became part of each chromosome when the mitotic spindle was developed in evolution. Concomitant with these changes in the genome, repetitive sequences in the form of constitutive heterochromatin appeared, probably as a result of large-scale duplication. The repetitive DNA's were kept through natural selection because of their importance in preserving these vital regions and in maintaining the structural and functional integrity of the nucleus. The association of satellite (or highly repetitive) DNA with constitutive heterochromatin is understandable, since it stresses the importance of the structural rather than transcriptional roles of these entities. Nuclear satellite DNA's have one property in common despite their species specificity, namely heterochromatization. In this sense the apparent species specificity of satellite DNA may be the result of natural selection for duplicated short polynucleotide segments that are nontranscriptional and can be utilized in specific structural roles.

https://science.sciencemag.org/content/sci/174/4015/1200.full.pdf

Heterochromatin, satellite DNA, and cell function. Structural DNA of eucaryotes may support and protect genes and aid in speciation.

All organisms suffer double-strand breaks (DSBs) in their DNA as a result of exposure to ionizing radiation. DSBs can also form when replication forks encounter DNA lesions or repair intermediates. The processing and repair of DSBs can lead to mutations, loss of heterozygosity, and chromosome rearrangements that result in cell death or cancer. The most common pathway used to repair DSBs in metazoans (non-homologous DNA end joining) is more commonly mutagenic than the alternative pathway (homologous recombination mediated repair). Thus, factors that influence the choice of pathways used DSB repair can affect an individual's mutation burden and risk of cancer. This review describes radiological, chemical, and biological mechanisms that generate DSBs, and discusses the impact of such variables as DSB etiology, cell type, cell cycle, and chromatin structure on the yield, distribution, and processing of DSBs. The final section focuses on nucleosome-specific mechanisms that influence DSB production, and the possible relationship between higher order chromosome coiling and chromosome shattering (chromothripsis).

/pdf/mechanisms-and-consequences-of-double-strand-dna-break-1ifqll4vnw.pdf

Mechanisms and Consequences of Double-Strand DNA Break Formation in Chromatin

A comprehensive review of the karyotype in plant systematics was pub­ lished by Lewitsky (83) 40 years ago under this same title. He was dissatis­ fied with the narrow use of meager karyological data and included his own more complete work on several genera of the Ranunculaceae subfamily Hel­ leboreae. He chose a group of genera showing distinct systematical relation­ ships both among and within the taxa with the further advantage that a detailed morphological study of the subfamily had been completed some 20 years before. There was thus a good opportunity for a comparison of the morphological and cytological findings. Lewitsky's general conclusions may be summarized as follows. The idea of the karyotype as a characteristic especially and exclusively applied to generic definitions or to any other systematic unit is not tenable. A particl1lar karyotype may be associated with a complex of characters circumscribing a family, tribe, genus, species, or race. When certain peculiarities such as size of chromosomes and basic number are concerned, their corrcspondcnce to higher taxonomic subdivisions does not imply that they did not derive from lower categories; it only indicates a greater phylogenetical stability of these peculiarities. Changes in chromosome morphology may lag behind or precede change in external phenotype. Close morphological similarity of taxa associ­ ated with great differences in the basic karyotype suggests that cytological differences have been by sudden fragmentations, translocations, etc. Partial correspondence of morphology and karyotype implies parallcl changes. From his studies in the Ranunculaceae, Lewitsky pointed out the general parallelism of more symmetrical b.ryotypes with primitive characters and asymmetrical karyotypes with specialized forms. Although reorganization of the karyotype has been discussed in terms of cytogenetics by several workero, White (162) was the first to present a lu­ cid account of karyotype evolution in animals, and Stebbins (140) has dis­ cussed the data for plants. The development of techniques for the study of vertebrate somatic chromosomes has brought about a veritable flood of ka­ ryotype papers, many of which are largely descriptive, showing the lack of a

The Karyotype in Systematics

The distribution of chromosome breakage points along human chromosomes was studied in lymphocytes irradiated in the G0-period with different doses of X-rays. The breakage points were found to be preferentially located in the so-called R-bands. The individual chromosomes were found to be involved in chromosome interchanges in proportion to their amount of R-band material with few exceptions.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1601-5223.1973.tb01104.x

Preferential location of X‐ray induced chromosome breakage in the R‐bands of human chromosomes

The evidence for mammalian germ cell mutagenicity induced by anticancer drugs is summarized. Primary attention is paid to the three major mouse germ cell mutagenicity tests- the dominant lethal, heritable translocation, and morphological specific locus tests- from which most germ cell mutagenicity data historically have been obtained. Of the 21 anticancer drugs reviewed, 16 have been tested in one or more of these three tests; with all 16 tested in the most common germ cell test, the male dominant lethal test, and 9 of the 16 also tested in the female dominant lethal test. The patterns of germ cell stage specificity for most of the anticancer drugs are similar, and generally resemble the patterns seen with other types of chemicals; however, some of the patterns are unique. For example, 2 of the 8 chemicals shown to induce dominant lethal mutations in female oocytes, do not induce dominant lethal mutations in male germ cells (adriamycin and platinol). Ten of the 16 chemicals tested in the dominant lethal test were positive in post-meiotic stages (spermatids through mature sperm), and seven also induced reciprocal translocations and/or specific locus mutations in post-meiotic stages. This propensity to induce mutations in post-meiotic stages has been observed with most mutagens. However, 5 of the anticancer drugs also induced dominant lethal mutations in spermatocytes (meiotic prophase cells) and one of them, 6-mercaptopurine, uniquely induced dominant lethal mutations exclusively in preleptotene spermatocytes. Finally, three of the anticancer drugs (melphalan, mitomycin C, procarbazine) are members of a very select group of chemicals shown to induce specific locus mutations in spermatogonial stem cells of mice. The implications for human risk are discussed.

Mutagenicity of anticancer drugs in mammalian germ cells.

The chromosome breaking effect of mitomycin C, methyl methanesulfonate, maleic hydrazide, 8-ethoxycaffeine and gamma rays on the primary root meristematic cells of Nigella damascena was studied. All the agents tested except 8-ethoxycaffeine, produced relatively fewer aberrations, when compared to Vicia faba cells, though both the species have nearly similar total chromosomal length. Test for the presence of heterochromatin in Nigella gave negative results and it is interpreted that the observed differences between Vicia and Nigella are due to the presence and absence of heterochromatin in their chromosome complements respectively. The role of heterochromatin in the production of chromosome aberrations and its significance in evolution are briefly discussed.

Heterochromatin and chromosome aberrations

The distribution of two break chromosome exchanges (dicentrics and centric rings) following gamma or neutron irradiation of resting seeds of rye, Secale cereale, has been investigated. The localisation of heterochromatin in the terminal ends of the chromosomes of rye facilitates distinguishing aberrations involving heterochromatin from others. Dicentrics found in or near heterochromatic regions were about 5 times more frequent after gamma irradiation and about 2.5 times more after neutron irradiation, than expected on a random distribution. The implications of these findings in relation to aberration formation are discussed.

G. Ahnström

Papers

Heterochromatin and chromosome aberrations

The localisation of radiation induced chromosome aberrations in relation to the distribution of heterochromatin in Secale cereale.