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Pertemuan 6

Biologi Sel dan


Molekul

Jumat, 11 Maret 2022


Tujuan Perkuliahan

1. Mahasiswa dapat menjelaskan struktur inti sel

2. Struktur kromosom dan DNA yang terintegrasi didalamnya


Inti Sel / Nukleus
Nukleus
● Merupakan tempat terdapatnya
kromosom, perlengkapan untuk replikasi
DNA dan transkripsi dan pemrosesan RNA
Nukleus
● The cell nucleus is surrounded by the nuclear envelope (also called nuclear membrane,
nucleolemma, or karyotheca).

● The material within the nuclear envelope is the nucleoplasm or karyoplasm.


● The components of the karyoplasm:
• DNA and its associated proteins, the chromatin
• skeletal elements, the nucleo- or karyoskeleton
• the fluid material surrounding the karyoskeleton and the chromatin, the nucleo- or karyosol

● Chromatid: one DNA chain and its associated proteins


● Chromosome: densely packed ´transport´ form of chromatin with characteristic shape during
cell division. In functional sense, the term is also used for the intermitotic phase.
The nuclear envelope: a double lipid bilayer that
encloses the genetic material in eukaryotic cells

The outer membrane is


continuous with the
endoplasmic reticulum
Nuclear membrane
- is a double lipid bilayer that encloses the
genetic material in eukaryotic cells.

- The nuclear membrane also serves as the


physical barrier, separating the contents of
the nucleus (DNA in particular) from the
cytoplasm.

- Many nuclear pores are inserted in the


nuclear membrane, which facilitate and
regulate the exchange of materials
(proteins such as transcription factors, and
RNA) between the nucleus and the
cytoplasm.
Nuclear pores in the nuclear envelope shown by cryofracture EM
nuclear membrane and nuclear poles, neurofilaments
The nuclear pore complex

The nuclear pore is made of


about 30-100 nucleoporin
proteins.
The mechanism of gating by the nuclear pore complex

Proteins that assist the nuclear


transport are called nuclear
transport receptors, NLS
receptors, or karyopherins
(importins into the nucleus and
exportins out of the nucleus).

First the NLS receptor (importin


alpha) recognizes the protein.
They reach the FG (Phe-Gly)
repeats of pore fibrils by which
they approach the central pore.
Importin beta binds to
nucleoporins within the central
pore and allows the passage of
the recognized proteins.
After crossing the pore, the
importins are removed from the
protein.
Nuclear lamina (the major component of nucleoskeleton) is
attached to the inside surface of the inner nuclear membrane
Electron microscopic image of the nuclear
lamina: a 2D mesh
The function of nuclear lamina: to stabilize
nuclear envelope and to bind chromatin

The nuclear lamina consists of 3 types of lamin proteins: A, B, and C.


Lamin A and C bind chromatin, whereas lamin B binds them to the nuclear membrane via lamin B receptor,
an integral membrane protein.
Phosphorylation of lamins leads to the disassembly of the structure during cell division.
A mutation of lamin A causes Hutchinson-Gilford progeria, an early aging syndrome.
The chromosomes have a territoreal
arrangement within the nucleus

Figure 5-18 Essential Cell Biology (© Garland Science 2010)


Nukleolus
● Salah satu subdomain pada nukleus
● Sel mamalia umumnya memiliki 1 – 5 nucleoli
● Nukleoli berdiameter 0,5 - 5 µm dan mengelilingi kluster gen penyandi
ribosomal RNA (rRNA) yang aktif ditranskripsi
● Merupakan tempat dimulainya biogenesis ribosom,
○ Transkripsi dan pemrosesan rRNA
○ Perakitan awal subunit ribosom
The structure of the nucleolus

NE - nuclear envelope
NO - nucleolar organizer, parts of the
chromosomes that organize nucleolus after
division
A - pars amorpha: DNA encoding rRNA
PF - pars fibrosa, primary rRNA transcripts
PG - pars granule, maturing ribosomal subunits
NAC - nucleolus-associated chromatin
The structure of the nucleoplasma

HC - Heterochromatin (electron dense granules): densely packed DNA without transcription


It has 2 forms, the constitutive HC, which is never transcribed, and is usually attached to
the nuclear envelope via the nuclear lamina. In contrast, facultative heterochromatin is
densely packed only in a particular cell type but could also be euchromatin.
EC - Euchromatin: less coiled DNA, the functional part of chromatin with intense mRNA synthesis
NU - Nucleolus: contains genes for ribosomal RNA
Nucleus

Euchromatine

Heterochromatine

Nucleolus

Heterochromatine

Euchromatine
Pattern of the nucleoplasma: heterochromatic - euchromatic

euchromatic: transcriptionally active  less condensed


often (but not always) is under active transcription
fibroblast neuron

heterochromatic: transcriptionally inactive  highly condensed


is a tightly packed form of DNA there is not RNA synthesis there (fibrocytes)
Special pattern in plasma cells
„clockwise appearance”
Kromosom dan
DNA
Kromosom
● Molekul DNA berukuran besar yang dapat mengalami propagasi secara stabil
saat terjadinya pembelahan sel
● Kromosom yang dapat berfungsi penuh (minimal) terdiri dari sekuens DNA
khusus berupa:
○ Sentromer – berperan dalam regulasi dan mempartisi kromosom saat mitosis dan meiosis
○ Telomer – melindungi molekul DNA pada bagian ujung dari kromosom dan memastikan proses
replikasi DNA
○ Titik awal replikasi DNA setiap 100.000 pasang basa
○ Gen
The compact structure of chromosomes during
mitosis
The 23 chromosome pairs of the human genom
Karyotype: chromosomes articially lined
FISH: fluorescent in situ hybridization up in order (e.g. for cytogenetic analysis)
Types of Chromosomes:
○ Autosomes = Body chromosomes or non sex
chromosomes ( humans have 44 or 22 pairs)
○ Sex Chromosomes = XX or XY (23rd pair for humans)
determines the sex of the offspring
Aberrant chromosomes are associated with
genetic deficits

An abnormally longer
chromosome 12 from a patient
with inherited ataxia

Figure 5-12 Essential Cell Biology (© Garland Science 2010)


Different levels of DNA packing

The 30 nm solenoid structure fiber


forms loops whose base is
attached to scaffold proteins.
Decondensation of these loops
allows the transcription of genes
they encode.
Different levels of DNA packing
● DNA -double-stranded helix is 2 nm thick
● Nucleosome - 11 nm thick
● 30nm chromatin fibre - 30 nm thick
● Chromatin loops - 300 nm thick
● Condensed chromatin - 700 nm thick
● Chromosome (mitotic) - 1400 nm thick
○ DNA is wrapped or looped using a protein matrix
The basic organizational unit of DNA in
chromosomes: the nucleosome
A linker histon (H1) determines the angle how linker DNA leaves
the core of the nucleosomes allowing further condensation

Figure 5-24 Essential Cell Biology (© Garland Science 2010)


Chromatin-remodeling complexes decondense the
chromatin making it accessible to other proteins for
replication, transcription and their regulations

Figure 5-27b Essential Cell Biology (© Garland Science 2010)


Histone modifications (and thus gene silencing)
may be inherited by daughter chromosomes – a
mechanism of epigenetic inheritance

Figure 5-32 Essential Cell Biology (© Garland Science 2010)


The structure of chromatin varies along a single
interphase chromosome

Figure 5-31 Essential Cell Biology (© Garland Science 2010)


Compaction
level in
euchromatin

During interphase
most chromosomal Compaction level
regions are in
euchromatic heterochromatin

Figure 10.21
10-64
Human DNA facts

● Genome = 3.2 billion base pairs of DNA across 24


different distinct chromosomes (22 automomes + X
+ Y)
● Take about 9.5 years to read out loud (without
stopping) the three billion pairs of bases in one
person's genome sequence
● Biologist simply say 23 pairs of chromosomes
● For diploid cells = 6.4 billion base pairs per somatic
cell
● Each ? is a single enormous DNA double-helix -
chromosome
Genome sizes
● Humans do not have the most chromosomes - Plants tend to have
these
● Humans do not have the largest gemone size - Fish tend to have
these
● An ant species has just 1 chromosome
● No real association between genome size and evolutionary
complexity - human near the middle some where
Reference
● Alberts: Molecular biology of the cell (5th edition)
● Slide by Viktoria Vereczki, M.D., Ph.D.

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