分子生物学 第十八章 染色体（Chromosomes）

1、Chapter 18,Chromosomes,18.1 Introduction18.2 Condensing viral genomes into their coats18.3 The bacterial genome is a nucleoid18.4 The bacterial genome is supercoiled18.5 Loops, domains, and scaffolds in eukaryotic DNA18.6 Specific sequence attach DNA to the matrix18.7 The contrast between interphase

2、 chromatin and mitotic chromosomes18.8 Lampbrush chromosomes are extended18.9 Polytene chromosomes form bands18.10 Polytene chromosomes expand at sites of gene expression18.11 The eukaryotic chromosome is a segregation device18.12 Centromeres have short DNA sequences in S. cerevisiae18.13 Centromere

3、s may contain repetitious DNA18.14 Telomeres are simple repeats that seal the ends of chromosomes18.15 Telomeres are synthesized by a ribonucleoprotein enzyme,Chromatin describes the condition of the chromosomal material during the interphase (between mitoses) of the cell cycle.Chromosome is a discr

4、ete unit of the genome carrying many genes. Each chromosome consists of a very long molecule of duplex DNA and an approximately equal mass of proteins. It is visible as a morphological entity only during cell division.Nucleoid is the compact body that contains the genome in a bacterium.Packing ratio

5、 is the ratio of the length of DNA to the unit length of the fiber containing it.,18.1 Introduction,Figure 18.1 The length of nucleic acid is much greater than the dimensions of the surrounding compartment.,18.1 Introduction,Capsid is the external protein coat of a virus particle.,18.2 Condensing vi

6、ral genomes into their coats,Figure 18.2 A helical path for TMV RNA is created by the stacking of protein subunits in the virion.,18.2 Condensing viral genomes into their coats,Figure 18.3 Maturation of phage lambda passes through several stages. The empty head changes shape and expands when it beco

7、mes filled with DNA. The electron micrographs show the particles at the start and end of the maturation pathway. Photographs kindly provided by A. F. Howatson.,18.2 Condensing viral genomes into their coats,Domain of a chromosome may refer either to a discrete structural entity defined as a region w

8、ithin which supercoiling is independent of other domains; or to an extensive region including an expressed gene that has heightened sensitivity to degradation by the enzyme DNAase I.Nucleoid is the compact body that contains the genome in a bacterium.,18.3 The bacterial genome is a nucleoid with man

9、y supercoiled loops,Figure 18.4 A thin section shows the bacterial nucleoid as a compact mass in the center of the cell. Photograph kindly provided by Jack Griffith.,18.3 The bacterial genome is a nucleoid with many supercoiled loops,Figure 18.5 The nucleoid spills out of a lysed E. coli cell in the

10、 form of loops of a fiber. Photograph kindly provided by Jack Griffith.,18.3 The bacterial genome is a nucleoid with many supercoiled loops,Figure 18.6 The bacterial genome consists of a large number of loops of duplex DNA (in the form of a fiber), each secured at the base to form an independent str

11、uctural domain.,18.3 The bacterial genome is a nucleoid with many supercoiled loops,MAR (matrix attachment site; also known as SAR for scaffold attachment site) is a region of DNA that attaches to the nuclear matrix.Nuclear matrix is a network of fibers surrounding and penetrating the nucleus.Scaffo

12、ld of a chromosome is a proteinaceous structure in the shape of a sister chromatid pair, generated when chromosomes are depleted of histones.,18.4 Loops, domains, and scaffolds in eukaryotic DNA,Figure 18.7 Histone-depleted chromosomes consist of a protein scaffold to which loops of DNA are anchored

13、. Photograph kindly provided by Ulrich K. Laemmli.,18.4 Loops, domains, and scaffolds in eukaryotic DNA,Figure 18.8 Matrix-associated regions may be identified by characterizing the DNA retained by the matrix isolated in vivo or by identifying the fragments that can bind to the matrix from which all

14、 DNA has been removed.,18.4 Loops, domains, and scaffolds in eukaryotic DNA,Chromocenter is an aggregate of heterochromatin from different chromosomes.Euchromatin comprises all of the genome in the interphase nucleus except for the heterochromatin.Heterochromatin describes regions of the genome that

15、 are permanently in a highly condensed condition are not transcribed, and are late-replicating. May be constitutive or facultative.,18.5 The contrast between interphase chromatin and mitotic chromosomes,Figure 18.9 The sister chromatids of a mitotic pair each consist of a fiber (30 nm in diameter) c

16、ompactly folded into the chromosome. Photograph kindly provided by E. J. DuPraw.,18.5 The contrast between interphase chromatin and mitotic chromosomes,Figure 18.10 A thin section through a nucleus stained with Feulgen shows heterochromatin as compact regions clustered near the nucleolus and nuclear

17、 membrane. Photograph kindly provided by Edmund Puvion.,18.5 The contrast between interphase chromatin and mitotic chromosomes,Figure 18.11 G-banding generates a characteristic lateral series of bands in each member of the chromosome set. Photograph kindly provided by Lisa Shaffer.,18.5 The contrast

18、 between interphase chromatin and mitotic chromosomes,Figure 18.12 The human X chromosome can be divided into distinct regions by its banding pattern. The short arm is p and the long arm is q; each arm is divided into larger regions that are further subdivided. This map shows a low resolution struct

19、ure; at higher resolution, some bands are further subdivided into smaller bands and interbands, e.g. p21 is divided into p21.1, p21.2, and p21.3.,18.5 The contrast between interphase chromatin and mitotic chromosomes,Chromomeres are densely staining granules visible in chromosomes under certain cond

20、itions, especially early in meiosis, when a chromosome may appear to consist of a series of chromomeres.Lampbrush chromosomes are the large meiotic chromosomes found in amphibian oocytes.,18.6 The extended state of lampbrush chromosomes,Figure 18.13 A lampbrush chromosome is a meiotic bivalent in wh

21、ich the two pairs of sister chromatids are held together at chiasmata (indicated by arrows). Photograph kindly provided by Joe Gall.,18.6 The extended state of lampbrush chromosomes,Figure 18.14 A lampbrush chromosome loop is surrounded by a matrix of ribonucleoprotein. Photograph kindly provided by

22、 Oscar Miller.,18.6 The extended state of lampbrush chromosomes,Bands of polytene chromosomes are visible as dense regions that contain the majority of DNACytological hybridization means the same as in situ hybridization.Interbands are the relatively dispersed regions of polytene chromosomes that li

23、e between the bands.Polytene chromosomes are generated by successive replications of a chromosome set without separation of the replicas.,18.7 Transcription disrupts the structure of polytene chromosomes,Figure 18.15 The polytene chromosomes of D. melanogaster form an alternating series of bands and

24、 interbands. Photograph kindly provided by Jose Bonner.,18.7 Transcription disrupts the structure of polytene chromosomes,Figure 18.16 Individual bands containing particular genes can be identified by in situ hybridization.,18.7 Transcription disrupts the structure of polytene chromosomes,Figure 18.

25、17 A magnified view of bands 87A and 87C shows their hybridization in situ with labeled RNA extracted from heat-shocked cells. Photograph kindly provided by Jose Bonner.,18.7 Transcription disrupts the structure of polytene chromosomes,Figure 18.18 Chromosome IV of the insect C. tentans has three Ba

26、lbiani rings in the salivary gland. Photograph kindly provided by Bertil Daneholt.,18.7 Transcription disrupts the structure of polytene chromosomes,Acentric fragment of a chromosome (generated by breakage) lacks a centromere and is lost at cell division.Centromere is a constricted region of a chrom

27、osome that includes the site of attachment (the kinetochore) to the mitotic or meiotic spindle.Kinetochore is the structural feature of the chromosome to which microtubules of the mitotic spindle attach. Its location determines the centromneric region.MTOC (microtubule organizing center) is a region

28、 from which microtubules emanate. The major MTOCs in a mitotic cell are the centrosomes.,18.8 The eukaryotic chromosome as a segregation device,Figure 18.19 Chromosomes are pulled to the poles via microtubules that attach to their kinetochores. They sister chromatids are held together until anaphase

29、 by glue proteins (cohesins). The centromere is shown here in the middle of the chromosome, but can be located anywhere along its length, including close to the end (acrocentric) and at the end (telocentric).,18.8 The eukaryotic chromosome as a segregation device,Figure 18.9 The sister chromatids of

30、 a mitotic pair each consist of a fiber (30 nm in diameter) compactly folded into the chromosome. Photograph kindly provided by E. J. DuPraw.,18.8 The eukaryotic chromosome as a segregation device,Figure 18.20 C-banding generates intense staining at the centromeres of all chromosomes. Photograph kin

31、dly provided by Lisa Shaffer.,18.8 The eukaryotic chromosome as a segregation device,Figure 18.21 The centromere is identified by a DNA sequence that binds specific proteins. These proteins do not themselves bind to microtubules, but establish the site a which the microtubule-binding proteins in tur

32、n bind.,18.8 The eukaryotic chromosome as a segregation device,Figure 18.22 Three conserved regions can be identified by the sequence homologies between yeast CEN elements.,18.8 The eukaryotic chromosome as a segregation device,Telomere is the natural end of a chromosome; the DNA sequence consists o

33、f a simple repeating unit with a protruding single-stranded end that may fold into a hairpin.,18.9 Telomeres are simple repeats that seal the ends of chromosomes,Figure 18.24 Telomerase positions itself by base pairing between the RNA template and the protruding single-stranded DNA primer. It adds G

34、 and T bases one at a time to the primer, as directed by the template. The cycle starts again when one repeating unit has been added.,18.10 Telomeres are synthesized by a ribonucleoprotein enzyme,Figure 18.23 The unusual behavior of telomeric fractions may be explained by G-G interactions. In the upper model a duplex hairpin is formed by G-G pairing. In the lower model, a G quartet is formed when 1 G is contributed by each of 4 repeating units.,18.9 Telomeres are simple repeats that seal the ends of chromosomes,Telomerase is the ribonucleoprotein enzym