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The male karyotype of Aulacocyclus tricuspis Kaup 1868 (Coleoptera, Scarabaeoidea, Passalidae, Aulacocyclinae) from New Caledonia contains an exceptionally high number of chromosomes, almost all of which are acrocentric (53,X1X2Y). Unlike the karyotypes of other species of the pantropical family Passalidae, which are principally composed of metacentric chromosomes, this karyotype is derived by fissions involving almost all the autosomes after breakage in their centromere region. This presupposes the duplication of the centromeres. More surprising is the X chromosome fragmentation. The rarity of X chromosome fission during evolution may be explained by the deleterious effects of alterations to the mechanisms of gene dosage compensation (resulting from the over-expression of the unique X chromosome in male insects). Herein, we propose that its occurrence and persistence were facilitated by (1) the presence of amplified heterochromatin in the X chromosome of Passalidae ancestor, and (2) the capacity of heterochromatin to modulate the regulation of gene expression. In A. tricuspis, we suggest that the portion containing the X proper genes and either a gene-free heterochromatin fragment or a fragment containing a few genes insulated from the peculiar regulation of the X by surrounding heterochromatin were separated by fission. Finally, we show that similar karyotypes with multiple acrocentric autosomes and unusual sex chromosomes rarely occur in species of Coleoptera belonging to the families Vesperidae, Tenebrionidae, and Chrysomelidae. Unlike classical Robertsonian evolution by centric fusion, this pathway of chromosome evolution involving the centric fission of autosomes has rarely been documented in animals. [ABSTRACT FROM AUTHOR]

Various studies suggest a tight relationship between chromosome rearrangements driving tumor progression and breaks at loci called common fragile sites. Most of these sites are induced after perturbation of the replication dynamics, notably by aphidicolin treatment. We have mapped the majority of these sites to the interface of R and G bands, which calls into question the previous assignment of aphidicolin-sensitive sites to R bands. This observation suggests that most of them correspond to loci that ensure the transition between early and late replicating domains. We show that calyculin A, which triggers chromosome condensation at any phase of the cell cycle but does not markedly impair replication, induces damage in the chromosomes of human lymphocytes treated in [G.sub.2] but not in [G.sub.1] phase. We demonstrate that these lesions colocalize with those induced by aphidicolin treatment. Hence, common fragile site stability is compromised, whether aphidicolin delays replication or calyculin A advances condensation. We also show that, in cells that go through an unperturbed S phase, completion of their replication and/or replication-associated chromatin reorganization occur all along the [G.sub.2] phase, which may explain their inability to condense properly after calyculin A treatment during this phase of the cell cycle. genome instability | DNA damage | calyculin A | aphidicolin | cell cycle

Mitotic chromosomes of butterflies, which look like dots or short filaments in most published data, are generally considered to lack localised centromeres and thus to be holokinetic. This particularity, observed in a number of other invertebrates, is associated with meiotic particularities known as "inverted meiosis," in which the first division is equational, i.e., centromere splitting-up and segregation of sister chromatids instead of homologous chromosomes. However, the accurate analysis of butterfly chromosomes is difficult because (1) their size is very small, equivalent to 2 bands of a mammalian metaphase chromosome, and (2) they lack satellite DNA/heterochromatin in putative centromere regions and therefore marked primary constrictions. Our improved conditions for basic chromosome preparations, here applied to 6 butterfly species belonging to families Nymphalidae and Pieridae challenges the holocentricity of their chromosomes: in spite of the absence of primary constrictions, sister chromatids are recurrently held together at definite positions during mitotic metaphase, which makes possible to establish karyotypes composed of acrocentric and submetacentric chromosomes. The total number of chromosomes per karyotype is roughly inversely proportional to that of non-acrocentric chromosomes, which suggests the occurrence of frequent robertsonian-like fusions or fissions during evolution. Furthermore, the behaviour and morphological changes of chromosomes along the various phases of meiosis do not seem to differ much from those of canonical meiosis. In particular, at metaphase II chromosomes clearly have 2 sister chromatids, which refutes that anaphase I was equational. Thus, we propose an alternative mechanism to holocentricity for explaining the large variations in chromosome numbers in butterflies: (1) in the ancestral karyotype, composed of about 62 mostly acrocentric chromosomes, the centromeres, devoid of centromeric heterochromatin/satellite DNA, were located at contact with telomeric heterochromatin; (2) the instability of telomeric heterochromatin largely contributed to drive the multiple rearrangements, principally chromosome fusions, which occurred during butterfly evolution. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+: poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] is a zinc-finger DNA-binding protein that detects specifically DNA strand breaks generated by genotoxic agents. To determine its biological function, we have inactivated both alleles by gene targeting in mice. Treatment of [PARP.sup.-/-] mice either by the alkylating agent N-methyl-N-nitrosourea (MNU) or by [Gamma]-irradiation revealed an extreme sensitivity and a high genomic instability to both agents. Following whole body [Gamma]-irradiation (8 Gy) mutant mice died rapidly from acute radiation toxicity to the small intestine. Mice-derived [PARP.sup.-/-] cells displayed a high sensitivity to MNU exposure: a [G.sub.2]/M arrest in mouse embryonic fibroblasts and a rapid apoptotic response and a p53 accumulation were observed in splenocytes. Altogether these results demonstrate that PARP is a survival factor playing an essential and positive role during DNA damage recovery.