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Regulation of chromosome dynamics in microorganisms
Regulation of chromosome dynamics in microorganisms Editorial overview: a sampler of current opinion Elizabeth H. Blackburn and Lucy Shapiro University of California, San Francisco, USA and Stanford University~ Stanford, USA ,, t
Current Opinion in Genetics and Development 1993, 3:697-698 The reviews in this issue of Current Opinion in Genetics and Development explore current progress in the regulation of chromosome dynamics. We include in our definition of dynamics: changes in DNA shape, movement of chromosomes and genomes between cells, and movement of regions of DNA between and within chromosomes by recombinatory mechanisms to form new functional units. We also include in our consideration of DNA dynamics, the formation of new sequences by various biosynthetic or mutagenic mechanisms. All of these different types of movement require regulation. Many of the organisms discussed are bacteria, as well as the so-called lower eukaryotes, largely because of the power of being able to combine their tractability as genetic systems with molecular and biochemical approaches. In addition, higher eukaryotes have in some cases also been considered in order to draw parallels. The reviews presented here could not represent every example of DNA dynamics that has been studied. In deciding on the areas to be covered in this issue of Current Opinion in Genetics and Development, we kept in mind a unifying theme: the fundamental mechanistic similarities underlying the strategies for regulation of DNA dynamics. The specialized biological function peculiar to each system is often the most obvious outward manifestation of a process, and may have sparked the original interest in it, but, as the articles in this issue make abundantly clear, the specialization is often superimposed on fundamentally similar regulatory strategies and mechanisms. Critical functions, such as the initiation of chromosome replication, turn out to be regulated in ways that are surprisingly similar in bacterial and eukaryotic systems. In particular, this regulation is coupled to transcriptional regulatory mechanisms in both bacteria and eukaryotes, as described in the articles by Marczynski and Shapiro (pp 775-782), Newlon and Theis (pp 752-758), and Kapler (pp 730--735). Changing the topology of DNA is critical, not only to transcriptional control (and vice versa), but also to chromosomal segregation in both prokaryotes and eukaryotes, as highlighted by the reviews by Wang and Lynch (pp 764-768) and Hiraga (pp 789--801). Even among the seemingly disparate mitochondrial genomes of yeast and mammals, control of replication shares common underlying mechanistic principles, as discussed in the review by Schmitt and Clay-
ton (pp 769-774). As Baker's review (pp 708-712) makes clear, a major mechanistic basis for control of bacteriophage Mu transposition is regulation of assembly of the transposition protein-DNA complex. Such regulation of multicomponent complexes, often bringing together distant regions of the DNA substrate, reviewed by Baker and by Landy (pp 699-707), provides important insights for regulation of transcription and replication as well. What is the fate of DNA as the cell divides? Whether the two daughter cells will both receive a complete copy of a chromosome depends not only on faithful, regulated replication, but also on successful chromosome segregation and cell division once a chromosome is completely replicated. Here, information from one source turns out to be surprisingly relevant to seemingly unrelated systems. Who would have guessed a few years ago that understanding the macromolecular components of muscle contraction would be important for dissecting the mechanism of bacterial chromosome movement? Yet the mukB gene product of Escherichia coli, required for chromosome segregation, is a coiled-coil protein with an A/GTP-binding domain which appears to belong to a motor protein superfamily, implying an active mechanism of chromosome separation, as described in Hiraga's review. With the involvement of such a putative motor protein, E. coli chromosome partition now appears to be more like eukaryotic chromosome movement. Cell division, which once looked so different between prokaryotes and eukaryotes, is now found to show much greater similarity than was previously thought. The reviews from Hiraga and from Lutkenhaus (pp 783-788) discuss the discoveries that the ftsZ gene product, required for cell division of bacteria, is tubulin-like, and that DNA replication is linked to control of cell septation. In fission yeast, yet another seemingly specialized aspect of DNA fate has emerged: the inheritance of specific DNA strands of a particular chromosome dictates cell fate, as described in the article by Klar (pp 745--751) - - this mechanism of ensuring the developmental nonequivalence of daughter cells may yet turn out to be more widespread than previously thought. There are even more unexpected examples of seemingly unrelated phenomena with related underlying molecular mechanisms: would anyone have had the prescience to suggest that formation of a peculiar branched RNA-DNA
(~ Current Biology Ltd ISSN 0959-437X
697
696
Regulation of chromosome dynamics in microorganisms molecule 'in the bacterium Myxococcus would share a common mechanism with the stabilization of eukaryotic chromosome ends? Yet reverse transcription is central to both these topics: the article by Inouye and Inouye (pp 713-718) deals with bacterial retrons, whose movement involves copying RNA into DNA by reverse transcription, and Shippen (pp 759-763) describes how reverse transcription is required to replicate the telomeres of chromosomes in eukaryotes ranging from the single cell to humans. Failure to correctly regulate telomere maintenance results in attrition of telomeric DNA, which can lead to mappropnate chromosomal recombinations and fusions. These types of recombination events constitute generally inadvertent types of chromosome dynamics, which, for the short term at least, must be avoided by appropriate regulation of telomere maintenance. On the other hand, under appropriate regulation, recombination is necessary for correct chromosome separation after replication in bacteria, as well as in meiosis, which is discussed by Hiraga, and by Atcheson and Esposito (pp 736-744). Appropriately regulated recombination, both site-specific and non site-specific, can productively reorganize DNA into new functional units. The new sequences resulting from mutagenesis in the SOS response can also be thought of as producing new functional genetic units, as presented by Murli and Walker (pp 719-725), and again the underlying themes cross between seemingly diverse systems and situations. The review by Atchison and Esposito shows that yeast and bacteria share fundamentally similar components in the mechanistic aspects of recombination, and that in eukaryotes, recombination is under developmental control during meiosis. But, the signals inducing meiotic recombination may share common features with those inducing recombination in the SOS re-
sponse in bacteria, as discussed by Murli and Walker - for example, double-stranded DNA breaks play central roles in the signalling pathways of these processes. Site-specific recombination is often under exquisitely fine control, as exemplified in the physiologically-controlled site-specific recombination of ~. and Mu bacteriophage, reviewed by Baker and Landy respectively, and in the developmentally-controlled DNA rearrangements in the eukaryotic ciliated protozoa and yeasts reviewed by Prescott (pp 726-729), by Kapler and by Klar. The reviews from Prescott and Kapler also show that the amplified genomes in the somatic macronuclei of ciliated protozoa result, not only from genomic remodelling, but also from some special twists in the control of replication - - here gene expression is regulated by developmentallyprogrammed gene amplification and by control of gene copy number in dividing cells, among other mechanisms. As a scientist trying to decide on a biological question or system to study, the temptation is sometimes to enter a popular area where results have recently been spectacular and in which current interest is high. Taking this road may add to the fun (and risk) of doing research; however, the reviews in this issue of Current Opinion in Genetics and Development should make it clear that one never knows in which system, and with which question, scientific gold will be found.
EH Blackburn, Departments of Microbiology and Immunology and Biochemistry and Biophysics, University of California, San Francisco, California, 94143-0414, USA. L Shapiro, Department of Developmental Biology, School of Medicine, Stanford University, California 94305-5427, USA.
Current Opinion in Genetics and Development 1993, 3:697-698 The reviews in this issue of Current Opinion in Genetics and Development explore current progress in the regulation of chromosome dynamics. We include in our definition of dynamics: changes in DNA shape, movement of chromosomes and genomes between cells, and movement of regions of DNA between and within chromosomes by recombinatory mechanisms to form new functional units. We also include in our consideration of DNA dynamics, the formation of new sequences by various biosynthetic or mutagenic mechanisms. All of these different types of movement require regulation. Many of the organisms discussed are bacteria, as well as the so-called lower eukaryotes, largely because of the power of being able to combine their tractability as genetic systems with molecular and biochemical approaches. In addition, higher eukaryotes have in some cases also been considered in order to draw parallels. The reviews presented here could not represent every example of DNA dynamics that has been studied. In deciding on the areas to be covered in this issue of Current Opinion in Genetics and Development, we kept in mind a unifying theme: the fundamental mechanistic similarities underlying the strategies for regulation of DNA dynamics. The specialized biological function peculiar to each system is often the most obvious outward manifestation of a process, and may have sparked the original interest in it, but, as the articles in this issue make abundantly clear, the specialization is often superimposed on fundamentally similar regulatory strategies and mechanisms. Critical functions, such as the initiation of chromosome replication, turn out to be regulated in ways that are surprisingly similar in bacterial and eukaryotic systems. In particular, this regulation is coupled to transcriptional regulatory mechanisms in both bacteria and eukaryotes, as described in the articles by Marczynski and Shapiro (pp 775-782), Newlon and Theis (pp 752-758), and Kapler (pp 730--735). Changing the topology of DNA is critical, not only to transcriptional control (and vice versa), but also to chromosomal segregation in both prokaryotes and eukaryotes, as highlighted by the reviews by Wang and Lynch (pp 764-768) and Hiraga (pp 789--801). Even among the seemingly disparate mitochondrial genomes of yeast and mammals, control of replication shares common underlying mechanistic principles, as discussed in the review by Schmitt and Clay-
ton (pp 769-774). As Baker's review (pp 708-712) makes clear, a major mechanistic basis for control of bacteriophage Mu transposition is regulation of assembly of the transposition protein-DNA complex. Such regulation of multicomponent complexes, often bringing together distant regions of the DNA substrate, reviewed by Baker and by Landy (pp 699-707), provides important insights for regulation of transcription and replication as well. What is the fate of DNA as the cell divides? Whether the two daughter cells will both receive a complete copy of a chromosome depends not only on faithful, regulated replication, but also on successful chromosome segregation and cell division once a chromosome is completely replicated. Here, information from one source turns out to be surprisingly relevant to seemingly unrelated systems. Who would have guessed a few years ago that understanding the macromolecular components of muscle contraction would be important for dissecting the mechanism of bacterial chromosome movement? Yet the mukB gene product of Escherichia coli, required for chromosome segregation, is a coiled-coil protein with an A/GTP-binding domain which appears to belong to a motor protein superfamily, implying an active mechanism of chromosome separation, as described in Hiraga's review. With the involvement of such a putative motor protein, E. coli chromosome partition now appears to be more like eukaryotic chromosome movement. Cell division, which once looked so different between prokaryotes and eukaryotes, is now found to show much greater similarity than was previously thought. The reviews from Hiraga and from Lutkenhaus (pp 783-788) discuss the discoveries that the ftsZ gene product, required for cell division of bacteria, is tubulin-like, and that DNA replication is linked to control of cell septation. In fission yeast, yet another seemingly specialized aspect of DNA fate has emerged: the inheritance of specific DNA strands of a particular chromosome dictates cell fate, as described in the article by Klar (pp 745--751) - - this mechanism of ensuring the developmental nonequivalence of daughter cells may yet turn out to be more widespread than previously thought. There are even more unexpected examples of seemingly unrelated phenomena with related underlying molecular mechanisms: would anyone have had the prescience to suggest that formation of a peculiar branched RNA-DNA
(~ Current Biology Ltd ISSN 0959-437X
697
696
Regulation of chromosome dynamics in microorganisms molecule 'in the bacterium Myxococcus would share a common mechanism with the stabilization of eukaryotic chromosome ends? Yet reverse transcription is central to both these topics: the article by Inouye and Inouye (pp 713-718) deals with bacterial retrons, whose movement involves copying RNA into DNA by reverse transcription, and Shippen (pp 759-763) describes how reverse transcription is required to replicate the telomeres of chromosomes in eukaryotes ranging from the single cell to humans. Failure to correctly regulate telomere maintenance results in attrition of telomeric DNA, which can lead to mappropnate chromosomal recombinations and fusions. These types of recombination events constitute generally inadvertent types of chromosome dynamics, which, for the short term at least, must be avoided by appropriate regulation of telomere maintenance. On the other hand, under appropriate regulation, recombination is necessary for correct chromosome separation after replication in bacteria, as well as in meiosis, which is discussed by Hiraga, and by Atcheson and Esposito (pp 736-744). Appropriately regulated recombination, both site-specific and non site-specific, can productively reorganize DNA into new functional units. The new sequences resulting from mutagenesis in the SOS response can also be thought of as producing new functional genetic units, as presented by Murli and Walker (pp 719-725), and again the underlying themes cross between seemingly diverse systems and situations. The review by Atchison and Esposito shows that yeast and bacteria share fundamentally similar components in the mechanistic aspects of recombination, and that in eukaryotes, recombination is under developmental control during meiosis. But, the signals inducing meiotic recombination may share common features with those inducing recombination in the SOS re-
sponse in bacteria, as discussed by Murli and Walker - for example, double-stranded DNA breaks play central roles in the signalling pathways of these processes. Site-specific recombination is often under exquisitely fine control, as exemplified in the physiologically-controlled site-specific recombination of ~. and Mu bacteriophage, reviewed by Baker and Landy respectively, and in the developmentally-controlled DNA rearrangements in the eukaryotic ciliated protozoa and yeasts reviewed by Prescott (pp 726-729), by Kapler and by Klar. The reviews from Prescott and Kapler also show that the amplified genomes in the somatic macronuclei of ciliated protozoa result, not only from genomic remodelling, but also from some special twists in the control of replication - - here gene expression is regulated by developmentallyprogrammed gene amplification and by control of gene copy number in dividing cells, among other mechanisms. As a scientist trying to decide on a biological question or system to study, the temptation is sometimes to enter a popular area where results have recently been spectacular and in which current interest is high. Taking this road may add to the fun (and risk) of doing research; however, the reviews in this issue of Current Opinion in Genetics and Development should make it clear that one never knows in which system, and with which question, scientific gold will be found.
EH Blackburn, Departments of Microbiology and Immunology and Biochemistry and Biophysics, University of California, San Francisco, California, 94143-0414, USA. L Shapiro, Department of Developmental Biology, School of Medicine, Stanford University, California 94305-5427, USA.