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1.
Genetic studies on heterochromatin in Drosophila melanogaster and their implications for the functions of satellite DNA 总被引:17,自引:2,他引:15
In Drosophila melanogaster the centromeric heterochromatin of all chromosomes consists almost entirely of several different satellite DNA sequences. In view of this we have examined by genetic means the meiotic consequences of X chromosomes with partial deletions of their heterochromatin, and have found that the amount and position of recombination on each heterochromatically deleted X is substantially different from that of a normal X. It appears that the amount of heterochromatin is important in modifying the centromere effect on recombination. — In all the deleted Xs tested, chromosome segregation is not appreciably altered from that of a nondeleted control chromosome. Thus satellite DNA does not appear to be an important factor in determining the regular segregation of sex chromosomes in Drosophila. Additionally, since X chromosomes with massive satellite DNA deficiencies are able to participate in a chromocenter within salivary gland nuclei, a major role of satellite DNA in chromocenter formation in this tissue is also quite unlikely. — In order to examine the mechanisms by which the amount of satellite DNA is increased or decreased in vivo, we have measured cytologically the frequency of spontaneous sister chromatid exchanges in a ring Y chromosome which is entirely heterochromatic and consists almost exclusively of satellite DNA. In larval neuroblast cells the frequency of spontaneous SCE in this Y is approximately 0.3% per cell division. Since there is no meiotic recombination in D. melanogaster males and since meiotic recombination in the female does not occur in heterochromatin, our results provide a minimum estimate of the in vivo frequency of SCE in C-banded heterochromatin (which is predominantly simple sequence DNA), without the usual complications of substituted base analogs, incorporated radioactive label or substantial genetic content. — We emphasise that: (a) satellite DNA is not implicated in any major way in recognition processes such as meiotic homologue recognition or chromocenter formation in salivaries, (b) there is likely to be continuous variation in the amount of satellite DNA between individuals of a species; and (c) the amount of satellite DNA can have a crucial functional role in the meiotic recombination system. 相似文献
2.
Interchromosomal Effects of Heterochromatic Deletions on Recombination in DROSOPHILA MELANOGASTER
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Masatoshi Yamamoto 《Genetics》1979,93(2):437-448
It is now known that partial deletions of the satellite sequences in X-chromosome heterochromatin result in a significant decrease in intrachromosomal recombination in the proximal region of the X chromosome of D. melanogaster (YAMAMOTO and MIKLOS 1978). It is important to ask then if the loss or gain of heterochromatin on the X also alters recombination in other chromosomes of the genome (interchromosomal effects). I have looked for such alterations by measuring recombination in chromosome 3. The results clearly indicate that the partial loss of X-chromosome heterochromatin not only decreases crossing over in the proximal region of the X chromosome itself, but also increases the frequency in chromosome 3, especially in the euchromatic regions around the centromere. Furthermore, the greater the deficiency of X heterochromatin, the higher is recombination in chromosome 3. This finding not only provides further evidence in support of the hypothesis that heterochromatin, in this case mainly composed of satellite DNA, regulates the recombination system, but it demonstrates that when the satellite content of one chromosome of the D. melanogaster genome is altered, there is an alteration in the crossover characteristics of other chromosomes in the same complement. If the amount of satellite DNA in a genome is being continuously altered, then one can predict that the recombination system is also being continually perturbed. Thus, the changing gene combinations produced indirectly by increases or decreases of heterochromatin are among the components available to organisms to break up or form new gene combinations upon which selection can act. 相似文献
3.
Aaron Mendez-Bermudez Liudmyla Lototska Melanie Pousse Florent Tessier Oliver Croce Chrysa
M Latrick Veronica Cherdyntseva Joe Nassour Jiang Xiaohua Yiming Lu Corinne Abbadie Sarantis Gagos Jing Ye Eric Gilson 《Nucleic acids research》2022,50(13):7493
Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53–TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2. 相似文献
4.
芽殖酵母(Saccharomyces cerevisiae)和裂殖酵母(Schizosaccharomyces pombe)是用来研究异染色质形成、细胞周期、DNA复制等重要细胞功能的理想单细胞真核生物.本文主要介绍这2种酵母中异染色质形成的机制.异染色质是一种抑制基因转录和DNA重组的特殊染色质结构.尽管在芽殖酵母和裂殖酵母中异染色质形成都需要组蛋白修饰,但异染色质建立的机制不同.在芽殖酵母中参与异染色质形成的主要蛋白是Sir1-4蛋白(其中Sir2为组蛋白H3去乙酰化酶),而组蛋白H3赖氨酸9甲基化酶Clr4和异染色质蛋白Swi6在裂殖酵母异染色质形成中起关键的作用.在这两个酵母中,参与异染色质形成的组蛋白修饰蛋白由DNA结合蛋白招募到异染色质.此外,裂殖酵母也利用RNA干扰系统招募组蛋白修饰蛋白. 相似文献
5.
《DNA Repair》2019
DNA double-strand breaks (DSBs) are particularly challenging to repair in pericentromeric heterochromatin because of the increased risk of aberrant recombination in highly repetitive sequences. Recent studies have identified specialized mechanisms enabling ‘safe’ homologous recombination (HR) repair in heterochromatin. These include striking nuclear actin filaments (F-actin) and myosins that drive the directed motion of repair sites to the nuclear periphery for ‘safe' repair. Here, we summarize our current understanding of the mechanisms involved, and propose how they might operate in the context of a phase-separated environment. 相似文献
6.
Transposable elements (TEs) play a fundamental role in the evolution of genomes. In Drosophila they are disproportionately represented in regions of low recombination, such as in heterochromatin. This pattern has been attributed to selection against repeated elements in regions of normal recombination, owing to either (1) the slightly deleterious position effects of TE insertions near or into genes, or (2) strong selection against chromosomal abnormalities arising from ectopic exchange between TE repeats. We have used defective non-long-terminal repeat (LTR) TEs that are "dead-on-arrival" (DOA) and unable to transpose in order to estimate spontaneous deletion rates in different constituents of chromatin. These elements have previously provided evidence for an extremely high rate of spontaneous deletion in Drosophila as compared with mammals, potentially explaining at least part of the differences in the genome sizes in these organisms. However, rates of deletion could be overestimated due to positive selection for a smaller likelihood of ectopic exchange. In this article, we show that rates of spontaneous deletion in DOA repeats are as high in heterochromatin and regions of euchromatin with low recombination as they are in regions of euchromatin with normal recombination. We have also examined the age distribution of five non-LTR families throughout the genome. We show that there is substantial variation in the historical pattern of transposition of these TEs. The overrepresentation of TEs in the heterochromatin is primarily due to their longer retention time in heterochromatin, as evidenced by the average time since insertion. Fragments inserted recently are much more evenly distributed in the genome. This contrast demonstrates that the accumulation of TEs in heterochromatin and in euchromatic regions of low recombination is not due to biased transposition but by greater probabilities of fixation in these regions relative to regions of normal recombination. 相似文献
7.
Telomeric satellite DNA functions in regulating recombination 总被引:18,自引:4,他引:14
Molecular and cytogenetical analyses of three sibling species of Australian grasshopper, Atractomorpha australis, A. species-1 and A. similis, resolves one of the long standing problems of highly repeated DNA. In this system satellite DNA functions in regulating the level and position of recombination, irrespective of whether the repeated DNA is located in telomeric or centric regions. — Even though the three species do not differ in their euchromatic genome sizes, their relative DNA contents are 1.00/1.10/ 1.41, the difference in genome size being due solely to visible centric or telomeric blocks of heterochromatin. — Antibiotic analytical and preparative ultracentrifugation, in situ hybridization and renaturation kinetic analyses reveal that a large cryptic satellite of A. similis constitutes the heterochromatic telomeric blocks of nearly all autosomes and that the DNA of this satellite is highly repeated. — Comparison of these grasshopper data with published literature of heterochromatic rearrangements in Drosophila and with heterochromatin distribution and recombination patterns in diploid plant species reveals that in every case heterochromatin is implicated in some form of alteration in the meiotic recombination system. 相似文献
8.
Addition of telomere-associated HeT DNA sequences "heals" broken chromosome ends in Drosophila 总被引:21,自引:0,他引:21
H Biessmann J M Mason K Ferry M d'Hulst K Valgeirsdottir K L Traverse M L Pardue 《Cell》1990,61(4):663-673
Stocks of D. melanogaster X chromosomes carrying terminal deletions (RT chromosomes) have been maintained for several years. Some of the chromosomes are slowly losing DNA from the broken ends (as expected if replication is incomplete) and show no telomere-associated DNA added to the receding ends. Two stocks carry chromosomes that have become "healed" and are no longer losing DNA. In both stocks the broken chromosome end has acquired a segment of HeT DNA, a family of complex repeats found only at telomeres and in pericentric heterochromatin. Although the HeT family is complex, the HeT sequence joined to the broken chromosome end is the same in both stocks. In contrast, the two chromosomes are broken in different places and have no detectable sequence similarity at the junction with the new DNA. Sequence analysis suggests that the new telomere sequences have been added by a specific mechanism that does not involve homologous recombination. 相似文献
9.
Singh A Henschel S Sperling K Kalscheuer V Neitzel H 《Cytogenetics and cell genetics》2000,91(1-4):253-260
It is generally thought that pairing and recombination between the X and Y chromosome in eutherian mammals is important for the occurrence of normal meiotic division and the production of functional gametes. Microtus agrestis is one of the examples whose giant and heterochromatin-rich sex chromosomes fail to establish a durable association at any stage of the first meiotic division in males. In contrast, in females, synapsis starts in the euchromatic short arm and pairing progresses unidirectionally and continues until both X chromosomes have paired completely, as can be demonstrated by the use of fluorescence in situ hybridization with a sequence confined to the non-centromeric, gonosomal heterochromatin. However, compared with euchromatin, this association is apparently ephemeral and breaks off precociously in the pachytene and metaphase I stages. We demonstrate that a middle repetitive element is localized interspersed in the noncentromeric heterochromatin of both X and Y, except the telomeric region of the Y. No differences could be detected at the molecular level between male and female DNA, indicating that at least the bulk of these elements are organized in the same manner on the X and Y. Our data imply that the loss of synapsis and recombination between the X and Y might have preceded the process of heterochromatin amplification in the course of Microtinae evolution. Since asynapsed elements are particularly susceptible to DNA strand breaks during prophase I, DNA repair of double-strand breaks involving heterochromatic segments of the X and Y could have resulted in translocations of larger segments from the X to the Y or vice versa during the course of chromosome evolution of the gonosomes, explaining the homology at the molecular level between the heterochromatin of the asynaptic X and Y in M. agrestis. 相似文献
10.
Chromatin structure and function are for a large part determined by the six members of the structural maintenance of chromosomes (SMC) protein family, which form three heterodimeric complexes: Smc1/3 (cohesin), Smc2/4 (condensin) and Smc5/6. Each complex has distinct and important roles in chromatin dynamics, gene expression and differentiation. In yeast and Drosophila, Smc6 is involved in recombinational repair, restarting collapsed replication forks and prevention of recombination in repetitive sequences such as rDNA and pericentromeric heterochromatin. Although such DNA damage control mechanisms, as well as highly dynamic changes in chromatin composition and function, are essential for gametogenesis, knowledge on Smc6 function in mammalian systems is limited. We therefore have investigated the role of Smc6 during mammalian spermatogonial differentiation, meiosis and subsequent spermiogenesis. We found that, during mouse spermatogenesis, Smc6 functions as part of meiotic pericentromeric heterochromatin domains that are initiated when differentiating spermatogonia become irreversibly committed toward meiosis. To our knowledge, we are the first to provide insight into how commitment toward meiosis alters chromatin structure and dynamics, thereby setting apart differentiating spermatogonia from the undifferentiated spermatogonia, including the spermatogonial stem cells. Interestingly, Smc6 is not essential for spermatogonial mitosis, whereas Smc6-negative meiotic cells appear unable to finish their first meiotic division. Importantly, during meiosis, we find that DNA repair or recombination sites, marked by γH2AX or Rad51 respectively, do not co-localize with the pericentromeric heterochromatin domains where Smc6 is located. Considering the repetitive nature of these domains and that Smc6 has been previously shown to prevent recombination in repetitive sequences, we hypothesize that Smc6 has a role in the prevention of aberrant recombination events between pericentromeric regions during the first meiotic prophase that would otherwise cause chromosomal aberrations leading to apoptosis, meiotic arrest or aneuploidies. 相似文献
11.
12.
Long terminal repeat (LTR) retrotransposons are the major DNA components of flowering plants. They are generally enriched in pericentromeric heterochromatin regions of their host genomes, which could result from the preferential insertion of LTR retrotransposons and the low effectiveness of purifying selection in these regions. To estimate the relative importance of the actions of these two factors on their distribution pattern, the LTR retrotransposons in Solanum lycopersicum (tomato) plants were characterized at the genome level, and then the distribution of young elements was compared with that of relatively old elements. The current data show that old elements are mainly located in recombination‐suppressed heterochromatin regions, and that young elements are preferentially located in the gene‐rich euchromatic regions. Further analysis showed a negative correlation between the insertion time of LTR retrotransposons and the recombination rate. The data also showed there to be more solo LTRs in genic regions than in intergenic regions or in regions close to genes. These observations indicate that, unlike in many other plant genomes, the current LTR retrotransposons in tomatoes have a tendency to be preferentially located into euchromatic regions, probably caused by their severe suppression of activities in heterochromatic regions. These elements are apt to be maintained in heterochromatin regions, probably as a consequence of the pericentromeric effect in tomatoes. These results also indicate that local recombination rates and intensities of purifying selection in different genomic regions are largely responsible for structural variation and non‐random distribution of LTR retrotransposons in tomato plants. 相似文献
13.
Centromeres are special structures of eukaryotic chromosomes that hold sister chromatid together and ensure proper chromosome segregation during cell division. Centromeres consist of repeated sequences, which have hindered the study of centromere mitotic recombination and its consequences for centromeric function. We use a chromosome orientation fluorescence in situ hybridization technique to visualize and quantify recombination events at mouse centromeres. We show that centromere mitotic recombination occurs in normal cells to a higher frequency than telomere recombination and to a much higher frequency than chromosome-arm recombination. Furthermore, we show that centromere mitotic recombination is increased in cells lacking the Dnmt3a and Dnmt3b DNA methyltransferases, suggesting that the epigenetic state of centromeric heterochromatin controls recombination events at these regions. Increased centromere recombination in Dnmt3a,3b-deficient cells is accompanied by changes in the length of centromere repeats, suggesting that prevention of illicit centromere recombination is important to maintain centromere integrity in the mouse. 相似文献
14.
Meiotic recombination is a deeply conserved process within eukaryotes that has a profound effect on patterns of natural genetic variation. During meiosis homologous chromosomes pair and undergo DNA double strand breaks generated by the Spo11 endonuclease. These breaks can be repaired as crossovers that result in reciprocal exchange between chromosomes. The frequency of recombination along chromosomes is highly variable, for example, crossovers are rarely observed in heterochromatin and the centromeric regions. Recent work in plants has shown that crossover hotspots occur in gene promoters and are associated with specific chromatin modifications, including H2 A.Z. Meiotic chromosomes are also organized in loop-base arrays connected to an underlying chromosome axis, which likely interacts with chromatin to organize patterns of recombination.Therefore, epigenetic information exerts a major influence on patterns of meiotic recombination along chromosomes, genetic variation within populations and evolution of plant genomes. 相似文献
15.
16.
Demakova OV Pokholkova GV Kolesnikova TD Demakov SA Andreyeva EN Belyaeva ES Zhimulev IF 《Genetics》2007,175(2):609-620
In polytene chromosomes of Drosophila melanogaster, regions of pericentric heterochromatin coalesce to form a compact chromocenter and are highly underreplicated. Focusing on study of X chromosome heterochromatin, we demonstrate that loss of either SU(VAR)3-9 histone methyltransferase activity or HP1 protein differentially affects the compaction of different pericentric regions. Using a set of inversions breaking X chromosome heterochromatin in the background of the Su(var)3-9 mutations, we show that distal heterochromatin (blocks h26-h29) is the only one within the chromocenter to form a big "puff"-like structure. The "puffed" heterochromatin has not only unique morphology but also very special protein composition as well: (i) it does not bind proteins specific for active chromatin and should therefore be referred to as a pseudopuff and (ii) it strongly associates with heterochromatin-specific proteins SU(VAR)3-7 and SUUR, despite the fact that HP1 and HP2 are depleted particularly from this polytene structure. The pseudopuff completes replication earlier than when it is compacted as heterochromatin, and underreplication of some DNA sequences within the pseudopuff is strongly suppressed. So, we show that pericentric heterochromatin is heterogeneous in its requirement for SU(VAR)3-9 with respect to the establishment of the condensed state, time of replication, and DNA polytenization. 相似文献
17.
18.
Ten per cent of mouse DNA occurs as a satellite band with a buoyant density lighter than that of the main band1. This satellite contains highly repetitious DNA2,3. It has been shown that the amount of satellite is markedly increased in DNA isolated from the heterochromatin fraction of mouse nuclei4. Furthermore, in situ hybridization studies have shown that satellite DNA is localized to the pericentromeric heterochromatin of all the mouse chromosomes except the Y5,6. These observations demonstrate an intimate association between mouse satellite DNA and heterochromatin and they raise the question: is all the DNA from mouse heterochromatin composed of satellite DNA or is a significant portion composed of non-satellite DNA? 相似文献
19.
Male meiosis, with special regard to the centromeric heterochromatin and to centromeric structure, has been studied in the salamander, Plethodon cinereus cinereus. In this salamander, n = 14. Early meiotic prophase proceeds as described by other authors. Pachytene is followed by a diffuse stage in which much of the chromosomal DNA becomes reorganized into fine lateral loops which spring from the bivalent axes. These loops can be seen along the bivalent axes as early as zygotene. Loops are maximally extended in the diffuse stage. The formation of diplotene bivalents involves a return of this extended DNA into the axes of the bivalents. — At leptotone, centromeric heterochromatin is in one or a few large masses. These masses break up during zygotene. At pachytene there is one mass of heterochromatin at the centromeric region of each bivalent. The heterochromatin remains condensed in the diffuse stage. During diplotene, centromeric heterochromatin becomes less conspicuous, and it is possible to see 4 centromere granules in each diplotene bivalent. These observations support the view that centromeres replicate at pre-meiotic S-phase when the associated hetero-chromatin is replicated. In the interphase before the 2nd division, the hetero-chromatin often forms a broken ring corresponding to the positions of the centromeres at the end of anaphase 1. There are 14 masses of heterochromatin in nuclei at prophase of the 2nd division. In spermatids, the heterochromatin appears as a single solid mass or a broken ring. 相似文献
20.
Keyur K. Adhvaryu Jordan D. Gessaman Shinji Honda Zachary A. Lewis Paula L. Grisafi Eric U. Selker 《Eukaryotic cell》2015,14(1):25-28
The cullin-4 (CUL4) complex DCDC (DIM-5/-7/-9/CUL4/DDB1 complex) is essential for DNA methylation and heterochromatin formation in Neurospora crassa. Cullins form the scaffold of cullin-RING E3 ubiquitin ligases (CRLs) and are modified by the covalent attachment of NEDD8, a ubiquitin-like protein that regulates the stability and activity of CRLs. We report that neddylation is not required for CUL4-dependent DNA methylation or heterochromatin formation but is required for the DNA repair functions. Moreover, the RING domain protein RBX1 and a segment of the CUL4 C terminus that normally interacts with RBX1, the E2 ligase, CAND1, and CSN are dispensable for DNA methylation and heterochromatin formation by DCDC. Our study provides evidence for the noncanonical functions of core CRL components. 相似文献