Molecular genetics is the study of molecules and mechanisms involved in genetic inheritance. Archival information molecules are long polymers of
deoxyribonucleic acid (
DNA) comprising
bases in specific sequence. The bases
adenine (A),
thymine (T),
cytosine (C), and
guanine (G), function as
codon triplets – sequences of three bases that code for specific
amino acids or for
translation initiation (start codons) or
termination (stop codons).
Uracil is substituted for
thymine in
RNA.
The segments of DNA that contain
protein-coding instructions are called
genes, and these gene sequences comprise a portion of the total
genome of a cell. The genome includes both the genes (coding-sequences, domains) and the non-coding sequences – both
exons, which include
open reading frames, and
introns.
Because the 64 possible combinations of G-A-T-C
code for only the 20 amino acids commonly found in proteins, the code is '
degenerate' (redundant) with more than one
triplet combination coding for each amino acid. (This code reduncancy provides hereditary stability by reducing
mutation errors.) The double helix of
DNA comprises paired nucleotide strands in which the nucleobases are
hydrogen bonded to
complementary bases in the adjacent chain.
Adenine pairs with
thymine or
uracil (A-TU), and
cytosine pairs with
guanine (CG).
During cellular
reproduction, strands of
archival DNA are copied or
replicated.
Transcription is the first step in gene expression – DNA instructions are converted into
mRNA codons,
rRNAs,
miRNAs, and
tRNAs.
Coding instructions of
nucleotide sequences in
archival DNA, which have been
transcribed and
processed into
mRNAs are then
translated into
polypeptides and proteins at
cytoplasmic ribosomes.
Translation is the ultimate step in gene expression, in which archival genetic instructions are converted into specified sequences of
amino acids in
peptides, polypeptides, and proteins.
In
prokaryotic cells – without a
nuclear membrane –
translation into
polypeptides and
proteins may begin prior to
termination of transcription. The molecular genetics of
eukaryotic cells is more complicated than that of
prokaryotes. Various molecules of ribonucleic acid (
RNA) participate in the
transcription of the
DNA code into
processed mRNA in a series of
RNA processing stages including
capping,
polyadenylation, and
pre-mRNA splicing.
Following
pre-mRNA processing, RNAs undergo extranuclear
transfer. Mature RNAs may undergo
post-transcriptional modulation (via
miRNAs) before
translation of the
archival DNA instructions into specific sequences of
amino acids in the
polypeptides and
proteins that participate in
cellular function and
structure.
Transfer RNAs (
tRNA) deliver specific
amino acids to the
cytoplasmic ribosomes along the
rough endoplasmic reticulum.
Ribosomal RNAs participate in assembly of
polypeptides and
proteins at ribosomes. Here RNAs serve as
ribozymes – non-proteinaceous
enzymes.
A number of processes are involved in
control of
cellular function through the maintenance of accuracy of
genetic inheritance – damage to DNA is
repaired, and faulty RNA is destroyed by
nonsense-mediated decay or
nonstop decay.
DNA damage may result from
replication errors, incorporation of mismatched nucleotides (
substitution errors – transitions and transversions), damage by oxygen radicals, hydroxyl radicals, ionizing or ultraviolet radiation, toxins, alkylating agents, and chemotherapy agents. A number of vital mechanisms
repair DNA damage to bases (including
C to T,
C to U, and
T U mismatch) and to strands, including
double strand breaks. All organisms,
prokaryotic and
eukaryotic, utilize at least three enzymatic excision-repair mechanisms for damaged bases:
base excision repair,
mismatch repair, and
nucleotide excision repair.
Given the importance of mRNA as an information-carrying molecule, faulty pre-mRNAs and mRNAs must be eliminated – they are
destroyed by
nonsense-mediated decay or
nonstop decay:
1. A
pre-mRNA made from a mutant gene usually has an exon junction complex (EJC) in the wrong position. This error activates
nonsense-mediated decay (NMD) and destroys the pre-mRNA before it can be used to make flawed proteins. There are at least two kinds of NMD: one requires the protein UPF2 and the other does not.
2.
Nonstop decay is mRNA turnover mechanism that has none of the properties of normal mRNA turnover or of
NMD. A multi-enzyme complex called the
exosome is important for nonstop decay. The exosome is the site for binding of a specific adapter protein called Ski7p. Nonstop decay shares
none of the
enzymes required for nonsense-mediated decay.
Just as cells
repair DNA, they must also maintain the
proteome by managing damaged proteins. Heat stress denaturates proteins, causing weakening of polar bonds and exposure of
hydrophobic groups. The
cellular stress response (heat-shock response) protects organisms from damage resulting from environmental
stressors such as heat, UV light, trace metals, and xenobiotics. Stress genes are activated to rapidly synthesize stress proteins, which are highly
conserved in
biological evolution and play similar roles in organisms from bacteria to humans. Normally, several constitutive stress proteins are present at low levels to function as
molecular chaperones, so as to facilitate folding, assembly, and distribution of newly synthesized proteins. For the environmentally stressed cell, stress proteins protect and repair vulnerable protein targets, and play a role in the
lysosomal and
ubiquitin protein degradation pathways (for removal of unsalvageable proteins). Thus, the cellular stress response performs orchestrated induction of key proteins necessary for cellular protein repair and degradation systems.
Topics:
item links : A :
adhesion molecules :
apoptosis : C :
cell biology :
chromosomes : D :
damage/repair DNA :
decay : E :
energy :
enzymes,
specific enzymes :
evo-devo :
evolution : G :
genome : M :
mechanisms of evolution :
metabolism :
molecular genetics :
mutation : P :
photosynthesis :
processing RNA :
proteins,
specific proteins : R :
regulation ·
cellular differentiation .
gene regulation .
metabolic regulation :
replication :
repair/damage DNA :
research :
RNA : S :
serial endosymbiosis theory :
signaling :
splicing : T :
tables :
transcription :
translation :
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