Genetics Final exam 4

Genetics

The most important model organism

mus musculus

one gene-one enzyme hypothesis

is pretty outdated

operon

a group of genes that operate together

Most all cells in your body have the

EXACT same code. Differentiation is due to differences in gene expression

world simplest animal

Trichoplax

Cellular differentiation

the process in which a stem cell alters from one type to a differentiated one

in eukaryotes, each gene has its own

promoter

Promoters

can have binding sites for both activator and repressor proteins

Enhancers

are distal regulatory elements that stimulate gene transcription

Insulators

can block the effect of enhancers

Core promoter

similar in every gene; Transcription factors bind

Regulatory Promoters

mix combos of regulatory elements bounds by activator proteins; Transcriptional activators bind

Distal promotor

the distal sequence upstream of the gene that may contain additional regulatory elements, often with a weaker influence than the proximal promoter

Cell signaling

The ability of a cell to receive, process, and transmit signals with its environment and with itself

Signaling cascade

is a series of chemical reactions that occur within a biological cell when initiated by a stimulus

histone

protein molecule around which DNA is tightly coiled in chromatin

primary protein structure

sequence of a chain of amino acids

secondary protein structure

alpha helix and beta pleated sheet

tertiary protein structure

3D folding pattern of a protein due to side chain interactions

quaternary protein structure

multiple protein subunits

domains

(distinct regions made up of specific
amino acid sequences) are associated with
unique functions in proteins

DNA binding motif

Specific activity of proteins which bind DNA and can interact with DNA to turn genes off or on

Zinc fingers

represent the majority of the DNA-binding motifs in eukaryotes, are involved in several processes

Leucine zipper:

the Helix-loop-helix (HLH) dimer, is shown bound to DNA fragment — each alpha helix represents a monomer

Replication protein A

is the major protein that binds to single-stranded DNA in eukaryotic cells.

SSB proteins

have motifs which favor SSDNA

proximal promoter elements

modulate the efficiency of basal levels of transcription

activators

act at core promoter

co-activator

protein binding

Regulatory regions

Carry consensus sequences to assist in gene regulation

Activators

increase transcription initiation

repressors

decrease transcription initiation

TFIID

the first general transcription factor to bind the promoter, binds to the TATA box through the TATA binding protein

Bacterial small regulator RNAs (sRNAs)

small bacterial RNAs that regulate gene expression

Riboswitch

(prokaryotic)A catalytic RNA whose activity responds to a small ligand

miRNAs

(eukaryotic) Small noncoding RNA gene that regulate gene expression

RNA interference (RNAi)

(eukaryotic) introduction of double-stranded RNA into a cell to inhibit gene expression

RNA silencing

The ability of a dsRNA to suppress expression of the corresponding gene systemically in plants

siRNA

(eukaryotic) Small interfering RNAs (21-24 nt typically) from a variety of sources that act to suppress gene expression

Cosuppression

The ability of a tansgene (usually in plants) to inhibit expression of the corresponding endogenous gene (requires sequence similarities)

RISC

A protein complex containing an Argonaute family protein with endonuclease activity

RITS

a form of RNA interference by which short RNA molecules trigger the downregulation of transcription of a particular gene or genomic region

DICER

facilitates the activation of RISC, which is essential for RNA interference

DNA methylation

adding a methyl group to DNA; deregulates

Chromatin Remodeling

ATP-dependent movement of nucleosomes relative to the DNA

Argonaute

common theme in eukaryotic RNA-directed chromatin modification is that small RNAs bound to Argonaute family proteins

Ubiquitination

Downregulates DNA transcription; reversible and does not result in destruction of histones

Phosphorylation

Upregulates gene expression associated with cell growth and division

CpG sites

regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction

CpG islands

CpG sites occur with high frequency in genomic regions

DNA methyltransferases

Enzymes that add a methyl group

Housekeeping genes

constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal circumstances

RNA-induced transcriptional silencing is mediated by what type of molecule?

Short RNA

Transcriptional silencing of TE elements was carried out by what type of protein and what type of RNA?

Argonaute and SiRNA(or piRNA)

Does acetylation of chromatin upregulate or downregulate gene expression?

Upregulate

What activity do housekeeping genes have?

Essential metabolic activities

leading cause of death in the West

Cancer

Cancer

a genetic disease at the somatic level, characterized by gene products derived from mutated or abnormally expressed genes

Cancer RARELY arises from single gene mutation but instead from

the accumulation of mutations in many genes

proliferation

Abnormal cell growth and division results in tumors

metastasis

Defects in normal restraints that prevent cells from spreading

Benign tumors

result from unregulated cell growth forming a multicellular mass that can be removed by surgery, causing no serious harm. (primary tumors)

Malignant tumors

result from cells that break loose and form secondary tumors

clonal

(both primary and secondary) originated from a common ancestral cell

Cancer stem cell hypothesis

Tumor cells that proliferate
give rise to cancer stem cells that have the capacity for self-
renewal

Cancer cells show higher than normal rates of

-Mutation
-Chromosomal abnormalities
-Genomic instability

Chronic myelogenous leukemia (CML)

The C-ABL gene on chromosome 9 is translocated into the BCR gene on chromosome 22 (Philadelphia chromosome)

G1/S checkpoints

monitor cell size and determine whether DNA damage has occured

G2/M checkpoint

physiological conditions are checked (once G1/S are passed) prior to mitosis

M

The formation of the spindle-fiber system and the attachment of spindle fibers to the kinetochores associated with the centromeres are monitored

cyclins and cyclin-dependent kinases (Cdks)

Two types of regulatory proteins are involved in cell cycle control

apoptosis

programmed cell death

Proto-oncogenes

genes whose products promote cell growth and division

oncogene

(a cancer-causing gene) is a mutated or aberrantly expressed proto-oncogene, a gain-of-function alteration

Tumor-suppressor genes

regulate cell-cycle checkpoints or initiate the process of apoptosis

ras genes

are mutated in more than 30 percent of human tumors and encode signal transduction molecules that are associated with the cell membrane and regulate cell growth and division

ras is a

proto-oncogene

p53 tumor-suppressor gene

mutated in more than 50 percent of all cancers, encodes a nuclear protein that acts as a transcription factor repressing or stimulating transcription of more than 50 different genes
(a lot p53=low levels of mutation)

The p53 protein becomes more stable and transcriptionally active in response to

chemical DNA damage, ionizing radiation , UV light

p53 protein two responses

Arrest cell cycle followed by DNA repair, or Apoptosis

RB1 (retinoblastoma 1) tumor-suppressor gene

Loss or mutation of both alleles of this gene contributes to the development of many cancers due to unregulated progression through the cell cycle

retinoblastoma protein (pRB)

a tumor-suppressor protein that controls the G1/S cell-cycle checkpoint by preventing passage into the S phase

Retroviruses

can contribute to the development of cancer in animals and humans

carcinogen examples

aflatoxin, nitrosamines, synthetic Pestides, or abestos

natural metabolism causes

oxidative products

E. coli

bacteria model organism

H. pylori

causes stomach acid

Recombinant DNA

used to copy or clone DNA, which allowed scientists to isolate and study specific DNA sequences

Restriction Enzymes

Cut DNA at Specific Recognition Sequences

Type II restriction enzymes

cleave within or at short specific distances from recognition site; most require magnesium (endonuclease)

endonucleases

cleaves nucleic acid strand at the middle

exonucleases

cleaves nucleic acid strands from the ends

EcoRI

is a type II restriction endonuclease enzyme isolated from species E. coli

plasmid

an extrachromosomal ds-DNA molecule that replicates independently from the chromosomes within bacterial cells, can be multiple copies per cell

blue colonies

empty vectors

white colonies

vectors with insert

Selection

usually "selects for" one type of cell (the desired cell type) - typically by killing all the others

Screening

usually refers to a method to distinguish/discriminate between (not live vs. dead) the desired and undesired cell type

Library screening

used to sort through a library and isolate specific genes of interest

probe

any DNA or RNA sequence that is complementary to the target gene of sequence to be identified