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31 Cards in this Set
- Front
- Back
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When can chromosomes be visualized?
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After S phase
(only if cells are dividing) Chromatin is condensed |
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Centromere
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Site of microtubule attachment during movement of sister chromatids to opposite poles in mitosis and meiosis
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Telomeres
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Protect DNA from shortening during replication
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Nucleosome
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Fundamental organizing unit of chromatin
An octamer of histones (pair of 4 subunits) H2A, H2B, H3, and H4 wrapped in about 157 bps are wrapped |
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H1 histone
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Binds the linker DNA between nucleosomes
40-50 bps (not part of the core nucleosome) When it binds, histone gets tighter, organizing nucleosomes such that solenoid form is favored |
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Organization of chromosomes
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DNA --> Nucleosome --> Beads on a string --> 30 nm fiber/solenoid --> DNA loops fastened on nuclear lamina --> higher structures
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Heterochromatin
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More compact form of DNA, containing mostly inactive genes
Not actively transcribed, close to membrane (e.g., centromere, telomere) |
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Euchromatin
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Looser form, composed of active genes that must interact with transcription factors and RNA polymerase etc. during transcription
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Are histones similar between species?
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YES!
Histones are <b> highly conserved </b>, meaning very important evolutionarily Very positively charged |
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Ubiquitin
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Small polypeptide with variety of signaling functions in cell
in DNA, adding ubiquitin to histone tails is a signaling mechanisms When ubiquitin is added to proteins, it signals them for degradation "serve as a signal for recognition by functionally relevant trans-acting factors and/or operate synergistically in conjunction with other post-translational modifications such as for instance acetylation." |
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Acetylation
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Acetyl groups get added to N terminal lysine residues, making them less positively charged, resulting in less affinity for DNA --> looser structures enhancing genetic activity
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Regulatory function of histones
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Histones are not totally buried inside DNA, ends protrude outside
They can get acetylated, methylated, phosphorylated, or ubiquitinated These influence affinity of nucleosome for non-histone proteins involved in packaging and gene expression |
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Histone code theory
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Histones get modified telling transcription factors what to do (e.g., phosphorylation can repress or activate transcription)
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Genes: definition
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entire DNA sequence required for synthesis of some useful RNA, including promoters, enhancers, UTRs, etc.
About 25% of genome, but open reading frames (exons only) are only 1.5% of genome In some cases different mature mRNAs are created by alternative splicing methosd End result is there are more proteins than there are genes that encode them. |
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Purpose of introns
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Several theories
Early theory: introns are ancient fossils and have been eliminated over time in lower forms like bacteria Late theory: introns emerged belatedly to help establish multi domain structure of protein genes during evolution May also serve purpose of interruption unequal crossovers between exons |
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Gene families
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Consist of multiple copies of genes having slightly different sequences, acquire different mutations, probably come from one ancestral gene
Probably resulted from unequal crossovers followed by separate mutations in each version over time. Ex. Globins, receptor proteins, protein kinases, HSP 70 family (heat shock) and B globin gene cluster |
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Human B-globin gene cluster
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Several genes close together encode a Beta type subunit protein, but some have higher affinities for oxygen and are expressed in fetal development only.
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Repetitive genes
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Very similar in sequence and lie close to each other (gene families are spread apart)
rRNAs expressed simultaneously Repetitive histone genes are also coordinately expressed in a burst of activity during S phase |
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Types of Interspersed Repeat Sequences of DNA
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1) Retrotransposons containing long-terminal repeats (LTRs)
2) Retrotransposons lacking LTRs LINES, SINES 3) Trinucleotide repeats |
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Retrotransposons containing long-terminal repeats (LTRs)
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Migrate via RNA intermediate involving reverse transcriptase and have LTR elements common to retroviruses
Have 250-600 bp LTR Similar to retroviruses, except <b> no proteins encoding envelope </b> so not infectious Get transcribed via RNA pol, then RNA intermediate is reversely transcribed, then DNA is inserted into place |
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Retrotransposons lacking LTRs
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make up 34% of genome!
Exist in two varieties - LINE and SINE |
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LINE
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Long Interspersed Nuclear Element
Encode a reverse transcriptase, most are inactive Probably jumped long time ago Factor VIII deficiency (type of hemophilia) caused when LINE jumps into the Factor VIII gene |
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SINE
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Short Interspersed Nuclear Element
LINES lacking protein-coding genes Move via an RNA intermediate with assistance of LINE-encoded enzymes Dominant class is Alu because it contains a cleavage site for the restriction enzyme AluI |
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What two processes were SINEs probably involved in evolutionarily?
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1) Double crossover (all Alu elements are homologous and can undergo crossover)
2) Double transcription Resulting from fragment flanked by two transposons Transposase excises SINE out and puts into gene 2 |
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Trinucleotide repeats
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Three base pair amplifications can occur inside exons, introns, control regions, and lead to numerous neurological conditions
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Huntington's
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expanded trinucleotide repeat disease which has tandemly repeated CAG sequences.
Give rise to unusually long Gln repeats within protein sequence Problems arise because of excess C, likely cause unusual, non B type structures or hairpins that cause polymerase pausing followed by slipping replication where same sequence is used for a template multiple times |
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Fragile X
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It is the second-most common cause of mental retardation after Down syndrome.
The name derives from the fact that the tip of the long arm of the X chromosome is held by a thin thread, then becomes even more delicate as a CCGn segment is aberrantly amplified. The n can be 400 to 1000 in afflicted individuals. The repeat is located in the 5’ UTR of the FMRP (fragile X mental retardation protein) gene. The mechanism of amplification is not clear but it may occur in somatic rather than germline cells. Furthermore, patterns of gene methylation (i.e., DNA methylation) is also unusually enhanced in this disease, causing the FMRP expression to decline. |
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Immunoglobulins (Ig) development
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This varied class of proteins derives from a variety of separated gene sequences that are physically moved into contiguous juxtaposition during differentiation of bone marrow cells as they develop into B lymphocytes.
Only one type of antibody is formed per cell, but the potential for >10^7 different antibodies exists in the gene array. The mechanism of gene rearrangement is curiously reminiscent of DNA transposition and may be an evolutionary vestige of that process. |
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Immunoglobulin G (IgG)
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Made of two heavy chains and two light chains
Each have constant and variable regions Two types of light chains (kapp and lambda) |
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Kappa light chain gene segments of IgG
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We shall use the kappa light chain gene segments to exemplify the organized, or programmed, gene rearrangement process that gives rise to the plethora of antibody types, one cell at a time. The variable (V) gene segments, numbering about 300, encode the first 95 amino acids of the variable region. The junction region (J), gene segments, numbering 4, encode the ~12-amino acid junction sequences, and the single C sequence encodes the constant region.
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Programmed gene rearrangement of IgG
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During maturation of a B lymphocyte, one V segment is joined with one J region, allowing for some imprecision in the junction nucleotides (another opportunity for variation). The gene is transcribed and the unwanted sequences between the J and C regions are spliced out, forming the mature mRNA for this particular kappa chain. There is the potential to form about 3000 kappa chains (in different cells) due to this gene rearrangement process. There is the possibility of producing 5000 different heavy chains as well, so the overall complexity is about 1.5x107.
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