Showing papers in "Journal of Genetics in 2000"

Evolutionary genetics: From molecules to morphology

Abstract: This is a collection of 32 articles, produced in honour of Prof. Richard Lewontin on the occasion of his sixtyfifth birthday. It is difficult to think of a better collection of comprehensive, timely, up-to-date, perceptive and highly readable reviews spanning the entire spectrum (from genes to societies) of evolutionary studies. But, then, nothing less would be acceptable for a volume in honour of Prof. Richard Lewontin: no reader of Journal of Genetics would be unaware of his very profound influence on every aspect of evolutionary biology during the last four decades. One of the most distinguished scientists of late eighteenth and early nineteenth centuries, Sir Humphry Davy, the most famous chemist in Europe during those years, discoverer of sodium and potassium, and founder of the field of electrochemistry, is said to have described Michael Faraday as his greatest discovery. In the same spirit is the quotation from Th. Dobzhansky reproduced at the beginning of the book: ‘[I]f I would not do anything else but to produce ... Dick Lewontin ... , I think my earthly existence would be justified.’ An exaggeration? Most certainly not—for this is how the editors most appropriately introduce Richard Lewontin (and I can neither resist nor do better than quoting them at length): ‘Scientists earn their reputation by making special contributions in a variety of ways. Some become known for a discovery that revolutionizes their science. Others are respected as intellectual leaders for significant contributions leading to sustained progress in their field. Still others become known for providing guidance and opportunity to and uniquely inspiring rapport with a large number of graduate students, writers and research colleagues. A rare few do all the above, and remarkably enough still find time to deal with the broader issues of epistemology, philosophy, history, and sociology of science. Richard Lewontin is one of these rare scientists.’ In fact, even a cursory look at the list of over 200 publications (in four or probably

Inheritance and segregation of exogenous genes in transgenic cotton.

Abstract: Three transgenic cotton varieties (lines) were chosen for the study of inheritance and segregation of foreign Bt (Bacillus thuringiensis toxin) andtfdA genes in cotton. The transformed cotton varieties CCRI 30 and NewCott 33B expressing the BtcryIA gene, and cotton line TFD expressing thetfdA gene were crossed with CCRI 19, CCRI 12 and Lumian 6. The results confirm inheritance and segregation of (i) the exogenous Bt gene in transgenic CCRI 30 and NewCott 33B, governing resistance to bollworm, and (ii) the exogenoustfdA gene in transgenic TFD, governing resistance to the herbicide 2,4-D. Both resistance characters were governed by a single dominant nuclear gene, and were not affected by cytoplasm. Our data support the conclusion that foreign traits encoded by single genes are inherited and expressed in Mendelian fashion in cotton. Our results also indicate that a practical backcross breeding program could be used to develop cotton cultivars combining one or more resistance traits from foreign and native gene sources.

Congruence of genomic and ethnolinguistic affinities among five tribal populations of Madhya Pradesh (India)

Abstract: The central Indian state of Madhya Pradesh is home to a large number of tribal populations of diverse linguistic and ethnic backgrounds. With a view to examining how well genomic affinities among tribal populations of this state correspond with their ethnic and linguistic affinities, we analysed DNA samples of individuals drawn from five tribes with diverse, but reasonably well-documented, ethnohistorical and linguistic backgrounds. Each DNA sample was scored at 16 biallelic DNA marker loci. On the basis of these data, genomic affinities among these populations were estimated. We have found an extremely good correspondence between the genomic and ethnolinguistic affinities.

Meiosis and speciation: A study in a speciatingMus terricolor complex

Abstract: The three chromosomal species of theMus terricolor complex possess 2n = 40 chromosomes. We show that their karyotypes differ in stable heterochromatin variations fixed in homozygous condition as prominent short arms in autosomes 1, 3 and 6. The three chromosomal species exhibit a high incidence of polymorphisms for Robertsonian fusions and pericentric inversions. Breeding experiments and histological analysis of testis show that heterozygosity for pericentric inversions and Robertsonian fusions had no effect on fertility. Meiotic analysis shows normal overall progression of meiosis in the heterozygotes, which is consistent with their normal gametogenesis. Nevertheless, both the inversion and fusion heterozygotes had undergone some alterations in the regular process of homologous synapsis, and it appeared that certain features of the meiotic system circumvented the potential negative effects of these polymorphic chromosomal rearrangements. The results indicate that the attributes of the meiotic system in a given organism could modulate the potential of a chromosomal rearrangement as reproductive barrier. The meiotic modulation hypothesis offers an explanation for the contradictory effects of the similar kinds of chromosomal mutations reported in different species.

The genetics of sheep

Abstract: This is the second of a series on genetics of some larger mammals. The pig was first, and the cow and horse have now appeared as the third and fourth in the series. I reviewed The genetics of the pig here (J. Genet. 1999, 78, 175), and must apologize for an error in confounding two local publishers: CAB International, who publish this series, and BIOS, to whom I wrongly attributed it. I had reviewed an equally fine book of similar size, shape and price. Both publishers are near Oxford, both use English printers, and both have unusually short intervals between the latest references and the date of publication. And both have, and justify, high prices. But this hardly excuses a reviewer from not reading the first page. The genetics of sheep follows that of the pig, continuing the logical progress of what are sheep; from where do they come; how have they diverged from the original stock; and what underlies their health, fertility, appearance and value. It starts well: ‘It seems very likely that sheep were among the earlier domesticated species and played a unique role in the development of several civilizations.’ They are even more versatile in their environments than the pig, better protected from heat and cold than pigs or cattle, and able to swim and negotiate precipitous terrain. Their diet varies from seaweed to cactuses. Their profound influence on the development of genetics is rarely appreciated: Mendel was born into a society dominated by sheep and how to breed them. They have even acted as an arbiter on a vowel sound in classical Greek. Without scrapie we may or may not have had BSE—but if the sheep are not to blame then, without them, we would be in a far darker gloom of ignorance. ‘Systematics and phylogeny’, ‘Domestication’, ‘Hair colour and texture’, and ‘Inherited disorders’ provide a solid foundation for the more specific chapters that follow. A remarkable feature of ‘Inherited disorders’, with its detailed list, is the absence or extreme rarity of some of the commoner human disorders, including neurofibromatosis, polycystic kidney disease, muscular

Understanding protein-protein interactions by genetic suppression

Abstract: Protein-protein interactions influence many cellular processes and it is increasingly being felt that even a weak and remote interplay between two subunits of a protein or between two proteins in a complex may govern the fate of a particular biochemical pathway. In a bacterial system where the complete genome sequence is available, it is an arduous task to assign function to a large number of proteins. It is possible that many of them are peripherally associated with a cellular event and it is very difficult to probe such interaction. However, mutations in the genes that encode such proteins (primary mutations) are useful in these studies. Isolation of a suppressor or a second-site mutation that restores the phenotype abolished by the primary mutation could be an elegant yet simple way to follow a set of interacting proteins. Such a reversion site need not necessarily be geometrically close to the primary mutation site.

Characterization of newly established colorectal cancer cell lines: correlation between cytogenetic abnormalities and allelic deletions associated with multistep tumorigenesis

Abstract: We have established a series of 20 colorectal cancer cell lines and performed cytogenetic and RFLP analyses to show that the recurrent genetic abnormalities of chromosomes 1, 5, 17 and 18 associated with multistep tumorigenesis in colorectal cancer, and frequently detected as recurrent abnormalities in primary tumours, are also retained in long-term established cell lines. Earlier studies by us and other investigators showed that allelic losses of chromosomes 1 and 17 in primary colorectal cancers predicted poorer survival for the patients (P = 0.03). We utilized the cell lines to identify specific chromosomal sites or gene(s) on chromosomes 1 and 17 which confer more aggressive phenotype. Cytogenetic deletions of chromosome 1p were detected in 14 out of the 20 (70%) cell lines, whereas allelic deletions for 1p using polymorphic markers were detected in 13 out of 18 (72%) informative cell lines for at least one polymorphic marker. We have performed Northern blotting, immunohistochemical staining (p53 mRNA, protein) and RFLP analysis using several probes including p53 and nm23. RFLP analysis using a total of seven polymorphic markers located on 17p and 17q arms showed allelic losses aroundthe p53 locus in 16 out of the 20 cell lines (80%), four of which were losses of thep53 locus itself. In addition, seven cell lines (out of nine informative cases) also showed losses of thenm23 gene, four with concurrent losses of thep53 locus, while the remaining three were homozygous. In addition, five out of seven cell lines withnm23 deletions were derived from hepatic metastatic tumours, and one cell line was obtained from recurrent tumour. A comparison between allelic deletions of 1p and functional loss ofnm23 gene revealed a close association between these two events in cell lines derived from hepatic metastasis. Following immunohistochemical staining, nine out of the twenty cell lines showed high levels (25–80%) of mutant p53, four showed intermediate levels (>20%), and seven had undetectable levels of the protein. Of these seven, four showed complete absence of mRNA. Of the remaining three cell lines one showed aberrant mRNA due to germline rearrangement of thep53 gene, whereas in two cell lines normal levels of mRNA were present. Nineteen of the 20 cell lines had normal germline configurations for thep53 gene, while one showed a rearrangement. These data suggest that functional loss ofp53 andnm23 genes accomplished by a variety of mechanisms may be associated with poor prognosis and survival. In addition, concurrent deletions of chromosome regions 17p, 17q and 1p were closely associated with high-stage hepatic metastatic disease. These cell lines with well-characterized genetic alterations and known clinical history provide an invaluable source of material for various biological and clinical studies relating to multistep colorectal tumorigenesis.

Induced mutation to monocotyledony in periwinkle, Catharanthus roseus, and suppression of mutant phenotype by kinetin

Abstract: A recessive EMS-induced mutation inherited in Mendelian fashion caused monocotyledonous embryo formation and seed germination on high salt medium inCatharanthus roseus. Availability during embryo development of exogenously supplied cytokinin kinetin suppressed the mutant phenotype. These observations suggest that, inC. roseus, (i) insufficiency in endogenous kinetin may lead to monocotyledonous embryo patterning and (ii) dicotyledonous embryo formation requires a critical amount of kinetin in certain cells of early embryos.

The p10 gene of Bombyx mori nucleopolyhedrosis virus encodes a 7.5-kDa protein and is hypertranscribed from a TAAG motif

Abstract: In baculovirus-based high-level expression of cloned foreign genes, the viral very late gene promoters of polyhedrin (polh)and p10 are extensively exploited. Here we report the cloning and characterization of the p10 gene from a local isolate of Bombyx mori nucleopolyhedrosis virus (BmNPV). The gene harbours a 213-bp open reading frame encoding a protein of 70 amino acids with a predicted molecular mass of 7.5 kDa. The BmNPV p10 showed deletion of a single A at a210 nucleotide compared to the prototype baculovirus, Autographa californica multinucleocapsid nucleopolyhedrosis virus (AcMNPV), p10 gene, resulting in a translational frameshift to generate a termination codon and consequently a truncated polypeptide instead of the 10-kDa protein. This protein P7.5 from BmNPV has a putative leucine zipper dimerization motif towards the N-terminal end and the central nuclear disintegration domain but the carboxy-terminal domain implicated in protein association for AEbrillar structure formation is absent.Phylogenetic analysis revealed that p10 is highly conserved among baculoviruses and the BmNPV strains are more closely related to AcMNPV than other baculoviruses.Thetranscription of p10 is regulated in a temporal manner, reaching maximal levels by 72 h post-infection. RNAase protection and primer extension analysis mapped the transcription start sites at i70 and i71 nt with respect to the ATG, within the conserved baculovirus late gene motif TAAG.The upstream region showed complete homology to the strong promoter of the AcMNPV p10, suggesting that this promoter from BmNPV could also be exploited for high-level expression of cloned foreign genes in silkworm cells or larvae.

Expression of the gene for large subunit of m-calpain is elevated in skeletal muscle from Duchenne muscular dystrophy patients

Abstract: Calpain is an intracellular nonlysosomal protease involved in essential regulatory or processing functions of the cell, mediated by physiological concentrations of Ca2+. However, in an environment of abnormal intracellular calcium, such as that seen in Duchenne muscular dystrophy (DMD), calpain is suggested to cause degeneration of muscle owing to enhanced activity. To test whether the reported increase in calpain activity in DMD results fromde novo synthesis of the protease, we have assessed the quantitative changes in mRNA specific for m-calpain. mRNA isolated from DMD and control muscle was analysed by dot blot hybridization using a cDNA probe for the large subunit of m-calpain. Compared to control a four-fold increase in specific mRNA was observed in dystrophic muscle. This enhanced expression of the m-calpain gene in dystrophic condition suggests that the reported increase in m-calpain activity results fromde novo synthesis of protease and underlines the important role of m-calpain in DMD.

A spectrum of genes expressed during early stages of rice panicle and flower development

Abstract: To unravel gene expression patterns during rice inflorescence development, particularly at early stages of panicle and floral organ specification, we have characterized random cloned cDNAs from developmental-stage-specific libraries. CDNA libraries were constructed from rice panicles at the stage of branching and flower primordia specification or from panicles undergoing floral organogenesis. Partial sequence analysis and expression patterns of some of these random cDNA clones from these two rice panicle libraries are presented. Sequence comparisons with known DNA sequences in databases reveal that approximately sixtyeight per cent of these expressed rice genes show varying degrees of similarity to genes in other species with assigned functions. In contrast, thirtytwo per cent represent uncharacterized genes. cDNAs reported here code for potential rice homologues of housekeeping molecules, regulators of gene expression, and signal transduction molecules. They comprise both single-copy and multicopy genes, and genes expressed differentially, both spatially and temporally, during rice plant development. New rice cDNAs requiring specific mention are those with similarity to COP1, a regulator of photomorphogenesis in Arabidopsis; sequence-speciAEc DNA binding plant proteins like AP2-domain-containing factors; genes that specify positional information in shoot meristems like leucine-rich-repeat-containing receptor kinases; regulators of chromatin structure like Polycomb domain protein; and also proteins induced by abiotic stresses.

Negative regulation ofUltrabithorax expression byengrailed is required for proper specification of wing development inDrosophila melanogaster

Abstract: In both vertebrates and invertebrates, homeotic selector genes confer morphological differences along the antero-posterior axis. However, insect wing development is independent of all homeotic gene functions, reflecting the ground plan of an ancestral pterygote, which bore wings on all segments. Dipteran insects such asDrosophila are characterized by a pair of wings in the mesothoracic segment. In all other segments, wing development is essentially repressed by different homeotic genes, although in the metathorax they are modified into a pair of halteres. This necessitates that during development all homeotic genes are to be maintained in a repressed state in wing imaginal discs. In this report we show that (i) the function of the segment polarity geneengrailed (en) is critical to keep the homeotic selector geneUltrabithorax (Ubx) repressed in wing imaginal discs, (ii) normal levels of En in the posterior compartment of haltere discs, however, are not enough to completely repressUbx, and (iii) the repression ofUbx byen is independent of Hedgehog signalling through which the long-range signalling ofen is mediated during wing development. Finally we provide evidence for a possible mechanism by whichen repressesUbx. On the basis of these results we propose thaten has acquired two independent functions during the evolution of dorsal appendages. In addition to its well-known function of conferring posterior fate and inducing long-range signalling to pattern the developing appendages, it maintains wing fate by keepingUbx repressed.

Stationary-state mutagenesis in Escherichia coli: a model

Abstract: Stationary-phase mutagenesis in nondividingE. coli cells exposed to a nonlethal stress was, a few years ago, claimed to be a likely case of a Lamarckian mechanism capable of producing exclusively useful mutations in a directed manner. After a heated debate over the last decade it now appears to involve a Darwinian mechanism that generates a transient state of hypermutagenesis, operating on a large number of sites spread over the entire genome, at least in a proportion of the resting cells. Most of the studies that clarified this position were on the reversion of a frameshift mutation present in alacI-lacZ fusion inE. coli strain FC40. Several groups have extensively examined both the sequence changes associated with these reversions and the underlying genetic requirements. On the basis of our studies on the genomic sequence analysis, we recently proposed a model to explain the specific changes associated with the reversion hotspots. Here we propose a more detailed version of this model that also takes into account the observed genetic requirements of stationary-state mutagenesis. Briefly, G:T/U mismatches produced at methylatable cytosines are preferentially repaired in nondividing cells by the very short patch mismatch repair (VSPMR) mechanism which is itself mutagenic and can produce mutations in very short stretches located in the immediate vicinity of these cytosine methylation sites. This mechanism requires a homologous or homeologous strand invasion step and an error-prone DNA synthesis step and is dependent on RecA, RecBCD and a DNA polymerase. The process is initiated near sequences recognized by Dcm and Vsr enzymes and further stimulated if these sequences are a part of CHI or CHI-like sequences, but a double-strand-break-dependent recombination mediated by the RecBCD pathways proposed by others seems to be nonessential. The strand transfer step is proposed to depend on RecA, RuvA, RuvB and RuvC and is opposed by RecG and MutS. The model also gives interesting insights into the evolution of theE. coli genome.

Conditions for the Trivers-Willard hypothesis to be valid: a minimal population-genetic model.

Abstract: The very insightful Trivers-Willard hypothesis, proposed in the early 1970s, states that females in good physiological conditions are more likely to produce male offspring, when the variance of reproductive success amongst males is high. The hypothesis has inspired a number of studies over the last three decades aimed at its experimental verification, and many of them have found adequate supportive evidence in its favour. Theoretical investigations, on the other hand, have been few, perhaps because formulating a population-genetic model for describing the Trivers-Willard hypothesis turns out to be surprisingly complex. The present study is aimed at using a minimal population genetic model to explore one specific scenario, viz. how is the preference for a male offspring by females in good condition altered when 'g', the proportion of such females in the population changes from a low to a high value. As expected, when the proportion of such females in good condition is low in the population, i.e., for low values of 'g', the Trivers-Willard (TW) strategy goes to fixation against the equal investment strategy. This holds true up to gmax, a critical value of 'g', above which the two strategies coexist, but the proportion of the TW strategy steadily decreases as 'g' increases to unity. Similarly, when the effect of well-endowed males attaining disproportionately high number of matings is more pronounced, the TW strategy is more likely to go to fixation. Interestingly, the success of the TW strategy has a complex dependence on the variance in the physiological condition of females. If the difference in the two types of conditions is not large, TW strategy is favoured, and its success is more likely as the difference increases. However, beyond a critical value of the difference, the TW strategy is found to be less and less likely to succeed as the difference becomes larger. Possible reasons for these effects are discussed.

Modulation of allele leakiness and adaptive mutability in Escherichia coli

Abstract: It is shown that partial phenotypic suppression of two ochre mutations (argE3 andlacZU118) and an amber mutation (inargE) by sublethal concentrations of streptomycin in anrpsL + (streptomycin-sensitive) derivative of theEscherichia coli strain AB1157 greatly enhances their adaptive mutability under selection. Streptomycin also increases adaptive mutability brought about by theppm mutation described earlier. Inactivation ofrecA affects neither phenotypic suppression by streptomycin nor replication-associated mutagenesis but abolishes adaptive mutagenesis. These results indicate a causal relationship between allele leakiness and adaptive mutability.

Gene therapy in inflammatory diseases

Abstract: Therapeutic interventions in autoimmune disorders are required to maintain a balance between suppressing an ongoing inflammatory process and maintaining normal function of essential immune responses. Multiple factorsÐ genetic, environmental and immunologicalÐcontribute to the heterogeneous manifestations associated with autoimmune disorders. Given the multifactorial nature of autoimmune disease, therapeutic approaches that involve the replacement of a single defective gene are obviously of minimal help in such diseases. However, the efficient delivery of therapeutic genes is a new, rapidly evolving investigational modality with promising applications in therapy of inherited and acquired diseases. This book brings together comprehensive information on the use of genes as vectors to deliver therapeutic gene products like cytokines and regulators of gene expression in various models of inflammatory diseases. The book principally focusses on chronic, inflammatory autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, lupus, multiple sclerosis and type I diabetes mellitus. The first chapter briefly discusses the limitations of conventional, pharmacological therapeutic approaches and serves to introduce certain basic concepts of gene therapy, including gene transfer strategies. The following three reviews focus on gene therapy of rheumatoid arthritis. Two papers detail successful therapeutic approaches involving vector-based delivery of anti-arthritic proteins, like the retroviral transfer of cytokines in murine models of rheumatoid arthritis. The third article in the section on rheumatoid arthritis describes the outcome of clinical trials performed in Germany and the USA on the use of retroviral transfer of cytokines as a therapeutic approach to rheumatoid arthritis. The subsection on rheumatoid arthritis is followed by reviews that focus on five other inflammatory disorders: allergic airway inflammation, Sjogren's syndrome, lupus, multiple sclerosis and type I diabetes mellitus. Research on gene therapy for inflammatory bowel disease, i.e. Crohn's disease, and ulcerative colitis is a striking omission from this group. These are followed by one review on the use of this therapeutic approach to regulate inflammation associated with organ transplantation or the immune response to alloantigens. Antigen-specific therapeutic approaches are by definition highly selective, therefore less deleterious to the system, but also require a precise knowledge of the immunologic target for the specific disease. Unlike the instability of recombinant cytokine proteins, cytokine-encoding gene therapy vectors allow for high levels of cytokine expression in vivo. This is perhaps best illustrated in the chapters on allergic airway in ̄ammation and multiple sclerosis, where the understanding of cytokine networks has been exploited for the treatment of disease. These studies have used the vast amount of information derived from basic research in these ®elds to attempt targeted delivery of cytokines to induce the desired goal of cytokine-induced immune deviation in established murine models of these two diseases. The reviews on speci®c diseases are followed by two general chapters that discuss the development of DNA vaccines and their application in in ̄ammatory diseases. The ®nal chapter in this book describes the application of gene transfer technology to study the contributions of speci®c cytokines to the development of articular pathophysiology. In general, the book covers a fairly wide canvas in the area of chronic inflammatory disease. There is an emphatic focus on rheumatoid arthritis, influenced perhaps by the completion of the first clinical trials on gene therapy for rheumatoid arthritis. The basic challenge of gene therapy still remains to develop specific, efficient and safe approaches for delivery of genetic material to specific cells. This problem is particularly challenging where the gene is large and complex and may require targeting to nuclei of relevant cells. Although some of the papers do mention the limitations of gene technology, the discussions are brief and there is need for a chapter devoted to this aspect, particularly for those not directly engaged in the field of molecular medicine. This book is recommended to clinicians and biologists with interests in applied aspects of immunology. # Indian Academy of Sciences

An improved procedure of mapping a quantitative trait locus via the EM algorithm using posterior probabilities

Abstract: Mapping a locus controlling a quantitative genetic trait (e.g. blood pressure) to a specific genomic region is of considerable contemporary interest. Data on the quantitative trait under consideration and several codominant genetic markers with known genomic locations are collected from members of families and statistically analysed to estimate the recombination fraction, θ, between the putative quantitative trait locus and a genetic marker. One of the major complications in estimating θ for a quantitative trait in humans is the lack of haplotype information on members of families. We have devised a computationally simple two-stage method of estimation of θ in the absence of haplotypic information using the expectation-maximization (EM) algorithm. In the first stage, parameters of the quantitative trait locus (QTL) are estimated on the basis of data of a sample of unrelated individuals and a Bayes’s rule is used to classify each parent into a QTL genotypic class. In the second stage, we have proposed an EM algorithm for obtaining the maximum-likelihood estimate of θ based on data of informative families (which are identified upon inferring parental QTL genotypes performed in the first stage). The purpose of this paper is to investigate whether, instead of using genotypically ‘classified’ data of parents, the use of posterior probabilities of QT genotypes of parents at the second stage yields better estimators. We show, using simulated data, that the proposed procedure using posterior probabilities is statistically more efficient than our earlier classification procedure, although it is computationally heavier.

Identification of four genes involved in suppression of the pre-mRNA splicing defect in the sng1-1/rhp6 - mutant of fission yeast

Abstract: Apart from the global regulators of silencing in the fission yeastSchizosaccharomyces pombe, namelyswi6, clr1,clr2, clr3, clr4 andrik1, the DNA repair generhp6 plays a unique role in mating-type silencing. Recently, we showed thatsng1-1, a mutation in the 5’ splice junction of the second intron of therhp6 gene, leads to derepression of both the silent locimat2 andmat3 in switching background. To address the mechanism ofrhp6 in silencing, we have isolated several extragenic suppressors of thesng1-1/rhp6 - mutation. These suppressors fall into four complementation groups and are referred to as suppressor ofrhp6: sur1, sur2, sur3 andsur4. Interestingly, reverse transcriptase polymerase chain reaction analysis of therhp6 transcript shows that in contrast to about <50% level of unsplicedrhp6 pre-mRNA in thesng1-1/rhp6 - mutant, there is a restoration of normal splicing to varying degrees in the suppressors. Thesur2 gene belongs to the AAA-ATPase family of proteins, with maximum homology to the SIN1-associated protein SAP1 ofSaccharomyces cerevisiae. We propose thatsur2, along withsur1, sur3 andsur4, may play an as yet uncharacterized role in pre-mRNA splicing.

sY116, a human Y-linked polymorphic STS

Abstract: During a study of deletions of Y-chromosomal DNA in infertile males, sY116, a Y-linked STS, showed different electrophoretic mobilities in three males, two infertile and one fertile. A study of this STS among 35 other normal males showed that this locus is polymorphic. sY1 16 has a polyA-rich stretch whose instability appears to be the most likely cause of this polymorphism. The possible usefulness of sY116 polymorphism in the detection of subtle genome-wide instabilities in some types of cancer is discussed.

Isolation of acdc28 mutation that abrogates the dependence of S phase on completion of M phase of the budding yeast cell cycle

Abstract: We have isolated a mutation in the budding yeastSaccharomyces cerevisisae CDC28 gene that allowscdc13 cells, carrying damaged DNA, to continue with the cell division cycle. Whilecdc13 mutant cells are arrested as largebudded cells at the nonpermissive temperature 37‡C, thecdc13 cdc28 double mutant culture showed cells with one or more buds, most of which showed apical growth. The additional buds emerged without the intervening steps of nuclear division and cell separation. We suggest that thecdc28 mutation abrogates a checkpoint function and allows cells with damaged or incompletely replicated DNA an entry to another round of cell cycle and bypasses the mitotic phase of the cell cycle.