The non-inherited genome

What is TP53?

The gene that encodes the p53 protein.

What is p53?

A protein that acts as a transcription factor to regulate genes involved in DNA repair, cell cycle arrest, and apoptosis.

What is the difference between TP53 and p53?

TP53 is the DNA gene, while p53 is the protein produced from that gene.

What is transcription?

The process of copying DNA into RNA.

What is translation?

The process of converting RNA into a protein.

What is a transcription factor?

A protein that binds DNA and controls whether a gene is turned on or off.

What is a promoter?

A region of DNA where transcription begins and where transcription machinery assembles.

How does a transcription factor turn on a gene?

By binding to DNA near the gene and helping recruit RNA polymerase to start transcription.

What is RNA polymerase?

An enzyme that synthesizes RNA from a DNA template.

What does it mean to "express" a gene?

To transcribe and translate it into a functional protein.

How does p53 activate gene expression?

It binds to DNA and promotes transcription of target genes.

What is p21?

A protein that inhibits cyclin-dependent kinases and stops the cell cycle.

How does p21 stop cell division?

It binds to CDKs and prevents them from driving the cell cycle forward.

What are cyclin-dependent kinases (CDKs)?

Proteins that control progression through the cell cycle.

What is the cell cycle?

The series of steps a cell goes through to grow and divide.

What does cell cycle arrest mean?

A توقف (halt) in cell division to allow repair or prevent damage.

What is apoptosis?

Programmed cell death that safely removes damaged cells.

What are Bax, Puma, and Noxa?

Proteins activated by p53 that promote apoptosis.

How do Bax, Puma, and Noxa cause apoptosis?

They disrupt mitochondria, releasing signals that activate caspases to destroy the cell.

What are caspases?

Enzymes that break down cellular components during apoptosis.

What role do mitochondria play in apoptosis?

They release cytochrome c, which triggers the cell death pathway.

What is cytochrome c?

A molecule released from mitochondria that activates apoptosis.

What is DNA damage?

Changes or breaks in DNA structure that can affect gene function.

What kinds of things cause DNA damage?

UV light, radiation, chemicals, and replication errors.

What is ATM?

A kinase that detects DNA damage and activates repair pathways.

What is a kinase?

An enzyme that adds phosphate groups to proteins.

What is phosphorylation?

The addition of a phosphate group to a protein, altering its function.

When is ATM activated?

When DNA damage, especially double-strand breaks, occurs.

What does ATM do to p53?

It phosphorylates and stabilizes p53 so it can accumulate.

What does ATM do to Mdm2?

It phosphorylates and inhibits Mdm2, preventing p53 degradation.

What does "stabilize p53" mean?

It prevents p53 from being degraded so it can build up and function.

What is Mdm2?

A protein that binds p53 and targets it for degradation.

What is protein degradation?

The breakdown of proteins into smaller components.

How does Mdm2 regulate p53?

It tags p53 for destruction and exports it out of the nucleus.

What is the ubiquitin-proteasome pathway?

A system that marks proteins for destruction and degrades them.

Why is p53 normally kept at low levels?

Because Mdm2 constantly targets it for degradation.

What happens to p53 after DNA damage?

It accumulates and activates genes for repair or apoptosis.

What determines whether a cell repairs or dies?

The level of DNA damage and amount of p53 activation.

What is DNA repair?

The process of fixing damaged DNA.

What is DNA polymerase?

An enzyme that synthesizes DNA, including during repair.

What is transformation?

The process by which a normal cell becomes cancerous.

How does p53 prevent transformation?

By stopping division, repairing DNA, or triggering cell death.

What is a tumor suppressor gene?

A gene that prevents uncontrolled cell growth.

Why is TP53 a tumor suppressor gene?

Because it prevents damaged cells from dividing.

What is a mutation?

A permanent change in the DNA sequence.

What is a missense mutation?

A mutation that changes one amino acid in a protein.

What is a nonsense mutation?

A mutation that creates a premature stop codon.

What is a dominant-negative mutation?

A mutant protein that interferes with the function of the normal protein.

How does mutant p53 act as dominant-negative?

It joins normal p53 in tetramers and blocks their function.

What is a tetramer?

A complex made of four protein subunits.

What is the structure of a p53 tetramer?

Four identical p53 proteins bound together.

Why is only 1/16 of p53 functional in some mutations?

Because only tetramers with four normal subunits work, and probability is (1/2)^4.

Can different cells have different mutations?

Yes, mutations occur independently in individual cells.

What is a single nucleotide polymorphism (SNP)?

A change in one nucleotide in DNA.

How are most p53 mutations classified?

As missense mutations that alter protein function.

Why do tumors benefit from mutant p53?

It disables normal p53 and can sometimes gain new pro-cancer functions.

Why can mutant p53 accumulate in cells?

It cannot activate Mdm2, so it is not degraded.

Why is high p53 level in cancer misleading?

Because the protein is present but non-functional.

What is an antigen?

A molecule recognized by the immune system, often foreign.

What is an antibody?

A protein that binds specifically to an antigen.

What is immunoprecipitation?

A technique using antibodies to isolate a protein and its binding partners.

What is SV40?

A virus that can cause tumors in cells.

What is the SV40 large T antigen?

A viral protein that binds and disables p53 and other tumor suppressors.

How do viruses make proteins?

They insert genetic material into host cells, which then produce viral proteins.

Do viruses enter cells?

Yes, they must enter cells to replicate.

How does large T antigen disable p53?

By binding to it and preventing it from functioning as a transcription factor.

How was p53 discovered?

As a protein bound to SV40 large T antigen during experiments.

What does 53 kDa mean?

The molecular weight (size) of the p53 protein.

What are proteins made of?

Chains of amino acids folded into specific shapes.

What determines a protein's function?

Its three-dimensional structure and interactions.

What is gene expression control?

The regulation of when and how genes are turned on or off.

Why is p53 called the guardian of the genome?

Because it protects cells from passing on damaged DNA.

What happens if p53 is lost or mutated?

Damaged cells continue dividing, increasing cancer risk.

What is Li-Fraumeni syndrome?

A genetic condition caused by inherited TP53 mutations leading to high cancer risk.

Why are epithelial cancers most common?

Epithelial cancers arise in tissues that line surfaces and cavities (e.g. skin, lungs, gut). These cells divide frequently and are highly exposed to environmental carcinogens, increasing the likelihood of mutations.

What are epithelial cells?

Cells that form sheets lining the surface of the body and internal cavities such as the skin, lungs, and digestive tract.

What is cellular transformation?

The process by which a normal cell acquires characteristics of a cancer cell, including uncontrolled proliferation, resistance to death, and the ability to form tumors.

What is the role of growth factors in cancer?

Normal cells require growth factors to divide, but cancer cells bypass this by producing their own (autocrine signalling), overexpressing receptors, or mutating signalling pathways.

What are endogenous sources of mutations?

Internal sources of DNA damage such as replication errors and reactive oxygen species produced during metabolism.

What are exogenous mutagens?

External agents that cause DNA damage, including UV radiation, ionising radiation, chemical carcinogens (e.g. tobacco smoke), and certain viruses (e.g. HPV).

What are the main types of mutations?

Point mutations (single base changes), insertions/deletions, copy number changes, and chromosomal rearrangements.

What is cancer?

A disease caused by mutations that disrupt normal control of cell proliferation, cell death, and DNA repair, leading to uncontrolled growth of cells derived from a single original mutated cell.

What is mitosis?

The process of cell division in which one cell duplicates its contents and divides into two identical daughter cells.

What is apoptosis?

Programmed cell death, a controlled process that removes damaged or unnecessary cells.

What is a benign tumor?

A non-invasive growth that does not spread to other tissues and is usually not life-threatening.

What is a malignant tumor?

A cancerous growth that invades surrounding tissues and can spread to distant parts of the body (metastasis).

What is a mutation?

A permanent change in the DNA sequence that can alter protein function or gene expression.

What is the wild-type sequence?

The most common or normal version of a gene found in a population.

What are silent mutations?

Mutations that do not change the amino acid sequence of a protein and usually have no effect on function.

What is a loss-of-function mutation?

A mutation that reduces or eliminates the activity of a protein; common in tumor suppressor genes.

What is a gain-of-function mutation?

A mutation that increases or alters the activity of a protein; common in oncogenes.

What is a dominant-negative mutation?

A mutation where the altered protein interferes with the function of the normal protein, often by forming non-functional complexes.

How does p53 act as a dominant-negative protein?

p53 functions as a tetramer, and a single mutant subunit within the complex can disrupt the function of the entire tetramer.

What is an oncogene?

A gene that promotes cell growth and survival when activated by mutation or overexpression.

What is a proto-oncogene?

A normal gene that becomes an oncogene when mutated or overexpressed.

What is a tumor suppressor gene?

A gene that normally inhibits cell division or promotes apoptosis; cancer develops when these genes lose function.

What are driver mutations?

Mutations that directly contribute to cancer progression by giving cells a growth advantage.

What are passenger mutations?

Mutations that occur during cancer development but do not contribute to tumor growth.

What is an actionable mutation?

A genetic change that can be specifically targeted with a therapy or used to guide treatment decisions.