Gene Regulation and Cancer

Gene Regulation

• At any given time, most of the thousands of genes in a cell are not needed. How do cells “turn on” (express) genes when needed and then turn them off (repress) again later?

• In cell differentiation, cells become specialized in structure and function.

• Certain genes are turned on and off in the process of gene regulation.

Gene Regulation in Prokaryotes• lac operons

– An operon includes• a cluster of genes with related functions and• the control sequences that turn the genes on or off.

– The first gene control mechanism understood was found in E. coli bacteria. It is a control for genes that make enzymes to break down lactose for energy. How does it work?

– Gene repressor proteins—bind to the beginning of a gene sequence and block transcription whenever lactose is NOT present.

– Lactose presentrepressor unbindsprotein expressed.• Operons are found ONLY in prokaryotes, not eukaryotes.

No lactose = no need to make enzymes to break lactose down for energy

Protein

mRNA

DNA

Operon turned off (lactose absent)

Active repressor

RNA polymerasecannot attach topromoter

Regulatory gene

Promoter

Operon

Genes for lactoseenzymes Operator

21

Operon turned on (lactose inactivates repressor)

Lactose

Protein

mRNA

Lactose enzymes

DNA

Translation

Inactiverepressor

RNA polymerasebound to promoter

Transcription

2

1

3

4

5

Lactose = need to make enzymes to break lactose down for energy

Gene Regulation in Eukaryotic Cells

• Eukaryotic cells have more complex gene regulating mechanisms with many points where the process can be turned on or off

• Each eukaryotic cell needs only a fraction of the total DNA information that is in it, so only the proper genes are expressed (“turned on”) and the others are repressed (“turned off”)

– Ex. Blood cells don’t “turn on” the same genes as your stomach cells do since they have different jobs to do than your stomach cells do

Gene Regulation in Eukaryotic Cells(continued)

Typical Eukaryotic Gene

EnhancerpromoterTATA boxstart codonGeneStop codon

Enhancers and Promoters—occur “upstream” of actual gene sequences. A complex array of proteins called transcription factors (TFs) bind to this region prior to transcription. These function by helping to unwind the helix at the gene site, attract the RNA polymerase or block (repress) binding by RNA.

Gene Regulation in Eukaryotic Cells(continued)

Typical Eukaryotic Gene

EnhancerpromoterTATA boxstart codonGeneStop codon

TATA box—almost all genes (both eukaryotic and prokaryotic) contain a sequence of TATAAA or TATAAT just before the start codon. This is thought to be an alignment checkpoint for RNA just before the gene is transcribed.

Developmental Genes

• A large set of genes in every eukaryotic organism are expressed only when that organism is first developing.

• Homeotic genes (aka hox genes)—a series of genes that control specialization and development in eukaryotic organisms’ organs and tissues.

• Surprisingly, the homeotic genes of all organisms are quite similar, even in organisms as diverse as humans and fruit flies. Scientists believe this is evidence of a common ancestor (hundreds of millions of years ago) for all eukaryotes.

The Genetic Basis of Cancer

– Cancer is a variety of diseases in which cells• experience changes in gene expression and• escape from the control mechanisms that normally

limit their growth and division.

Genes that Cause Cancer

– As early as 1911, certain viruses were known to cause cancer.

– Oncogenes are• genes that cause cancer and are found in viruses

Oncogenes

– Proto-oncogenes are• normal genes with the potential to become oncogenes,• found in many animals, and• often genes that code for growth factors, proteins that

stimulate cell division (and if these growth factors become hyperactive, cancer may result

– A cell can acquire an oncogene• from a virus or • from the mutation of one of its own proto-oncogenes.

Tumor-Suppressor Genes

– Tumor-suppressor genes• inhibit cell division,• prevent uncontrolled cell growth, and• may be mutated and contribute to cancer.

– Researchers have identified many mutations in both tumor-suppressor and growth factor genes that are associated with cancer.

Defective,nonfunctioningprotein

Cell divisionunder control

(b) Uncontrolled cell growth (cancer)

Normal growth-inhibiting protein

Cell division notunder control

(a) Normal cell growth

Tumor-suppressor gene Mutated tumor-suppressor gene

“Inherited Cancer”

– Most mutations that lead to cancer arise in the organ where the cancer starts.

– In familial or inherited cancer, • a cancer-causing mutation occurs in a cell that gives

rise to gametes and• the mutation is passed on from generation to

generation.

Cancer Risk and Prevention

– Cancer• is the second leading cause of death (after heart

disease) in most industrialized countries and• can be caused by carcinogens, cancer-causing agents,

found in the environment, including– tobacco products,– alcohol, and– exposure to ultraviolet light from the sun.