Basic Genetics and Cell Cycle Overview

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which term describes a variant form of a gene?

Gene

Chromosome

Nucleotide

Allele (correct)

What term refers to tightly packed DNA?

Chromatid

Chromosome (correct)

Nucleotide

Allele

Which of the following is the basic building block of DNA?

Chromosome

Gene

Chromatid

Nucleotide (correct)

What contains the instructions to make a particular protein?

Gene Signup and view all the answers

Which structure typically possesses two arms?

Chromosome Signup and view all the answers

How many chromosomes do most human cells contain?

46 Signup and view all the answers

How many chromatids does a human chromosome usually have during cell division?

2 Signup and view all the answers

What component is essential for the transition through the cell cycle?

Cyclins Signup and view all the answers

What characterizes Lynch syndrome colorectal carcinoma concerning microsatellite instability?

It is characterized by microsatellite instability-high (MSI-H) Signup and view all the answers

Which genetic process is primarily affected by the absence of functional BRCA1 and BRCA2 proteins?

Homologous recombination for DNA repair Signup and view all the answers

What type of mutations are primarily responsible for the increase in microsatellite instability?

Frameshift mutations Signup and view all the answers

Which gene mutation account for a significant percentage of hereditary breast cancers?

BRCA1 and BRCA2 Signup and view all the answers

Which class of regulatory genes is specifically responsible for inhibiting cell growth and reducing oncogenic potential?

Tumor suppressor genes Signup and view all the answers

Which gene family is primarily involved in regulating apoptosis?

Bcl-2 family Signup and view all the answers

Which specific chromosomal translocation is associated with chronic myelogenous leukemia?

t(9;22) Signup and view all the answers

What is a common cause for the majority of chromosomal translocations?

Erroneous repair of DNA double-strand breaks Signup and view all the answers

What characterizes the evasion of programmed cell death in Follicular Lymphoma?

Overexpression of Bcl-2 Signup and view all the answers

What type of genetic damage is primarily associated with the CRTC1-MAML2 translocation in mucoepidermoid carcinoma?

Chromosomal translocations Signup and view all the answers

What primarily determines the unique physical features of an individual?

Variations of a single gene known as alleles Signup and view all the answers

Which of the following components is NOT considered a target of gene mutation in carcinogenesis?

Mitochondrial genes Signup and view all the answers

How many total chromosomes are present in most human cells?

46 Signup and view all the answers

Which of the following best describes a gene?

A sequence of nucleotides encoding a single protein Signup and view all the answers

The sequence of which components determines the information encoded within DNA?

Nucleotide bases Signup and view all the answers

What is the primary purpose of DNA replication preceding cell division?

To create two identical copies of DNA Signup and view all the answers

Which of the following statements regarding alleles is correct?

Alleles have slight variations in their DNA base sequence. Signup and view all the answers

What role do tumor suppressor genes play in relation to carcinogenesis?

They help prevent tumor formation by regulating cell growth. Signup and view all the answers

What is the primary role of tumor suppressor genes in cellular processes?

To inhibit cell growth Signup and view all the answers

According to the Knudson 'two-hit' hypothesis, what must occur for tumor development involving tumor suppressor genes?

Both alleles must be mutated Signup and view all the answers

Which of the following cancer predisposition syndromes is characterized by a germline mutation in the APC gene?

Familial adenomatous polyposis Signup and view all the answers

What is the consequence of germline mutations in tumor suppressor genes?

Increased risk for tumor development Signup and view all the answers

Which protein is directly encoded by the TP53 gene and plays a crucial role in regulating cell cycle and DNA repair?

p53 Signup and view all the answers

In patients with familial retinoblastoma syndrome, what is the status of one allele of the RB gene?

It is inactive in every cell of the body. Signup and view all the answers

Which tumor suppressor gene is involved in the regulation of the Hedgehog signaling pathway?

PTCH1 Signup and view all the answers

What is the significance of the deletions in 22q region concerning meningiomas?

They indicate errors in DNA replication. Signup and view all the answers

Which signaling pathway is downregulated by the APC tumor suppressor?

Wnt/$eta$-catenin signaling pathway Signup and view all the answers

Which of the following best describes a somatic mutation?

It affects non-germ cells only. Signup and view all the answers

Which tumor suppressor is frequently mutated in human cancers and acts as the guardian of genomic stability?

TP53 Signup and view all the answers

How does MDM2 negatively regulate the p53 protein?

Through overexpression Signup and view all the answers

Which condition is characterized by multiple adenomatous colonic polyps and high risk for colorectal carcinoma due to APC mutations?

Gardner syndrome Signup and view all the answers

Which gene is often mutated in liposarcoma leading to the overexpression of proteins that promote cell cycle progression?

CDK4 Signup and view all the answers

What is the main risk factor for developing retinoblastoma at a younger age?

Germline mutation of RB Signup and view all the answers

Study Notes

Basic Genetics

A gene is a DNA sequence that provides instructions for making proteins
Humans have 20,000-25,000 genes.
Each person has two copies of each gene, one from each parent
Alleles are variations of a single gene
Most genes are the same in all people, but <1% of genes vary slightly between people
Chromosomes are tightly packed DNA, humans have 46 chromosomes (23 pairs) in most cells
Nucleotides are the building blocks of DNA

Cell Cycle

The cell cycle is a series of events that occur in a cell as it prepares for division (growth) and then divides into two daughter cells
The cell cycle is a highly orchestrated balance of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors
- Cyclins (proteins) turn on kinases
- CDK inhibitors inhibit CDK function
- G0 (resting) phase: where the cell spends most of its time
Signal transduction pathways are series of molecular events.
- Proteins encoded by genes participate in signaling
- Abnormalities in tumor suppressor genes can lead to failure of growth inhibition
  - Loss of function mutations means the proteins are not able to function properly

Knudson’s Two-Hit Hypothesis

Humans have two alleles (copies) of a gene
For tumor suppressor genes, both alleles must be mutated prior to tumor development
One allele can still ‘pick up the slack’ for its mutated counterpart
If one allele is mutated, a person may be predisposed to cancer
There are many cancer predisposition syndromes characterized by germline mutations in tumor suppressor genes
Germline mutation: mutated gene in egg or sperm (germ cells), can be passed to offspring
Somatic mutation: mutation in a cell of the body other than a germ cell, cannot be passed to offspring
Patients with germline mutations in tumor suppressor genes are at markedly elevated risk for tumor development
One allele of a given tumor suppressor gene is already inactivated in every cell in the body

Tumor Suppressor Genes

RB Regulates expression of genes necessary for dividing cells to pass through G1/S cell cycle checkpoint.
- Inactivated in most human cancers
PTCH Regulates Hedgehog signaling pathway
- Provides negative regulation of hedgehog signaling pathway
- Mutated in Gorlin Syndrome (nevoid basal cell carcinoma syndrome)
APC Downregulates Wnt/β-catenin signaling pathway
- Mutations in APC gene are present in 70-80% of sporadic colorectal carcinoma
- Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome with germline APC mutations
- Individuals with FAP develop hundreds of adenomatous colonic polyps by age 30, with a risk for transformation to colorectal carcinoma.
TP53 Regulates cell cycle progression, DNA repair, cellular senescence, apoptosis
- Most frequently mutated gene in human cancers
- Monitors DNA damage and cell stress
- Induces growth arrest and DNA repair, or apoptosis if DNA cannot be repaired

Other Mechanisms of Tumor Suppressor Gene Inactivation

Gene deletions
- Example: NF2 gene (22q) is commonly deleted in meningiomas
Gene amplifications
- Example: MDM2 gene (12q13-15) is often amplified in liposarcomas - MDMN2 is a negative regulator of p53 - Overexpression of MDM2 can mimic the effect of a TP53 mutation
Chromosomal translocations
- Can occur during erroneous repair of DNA double-strand breaks
- Example: Philadelphia chromosome (t(9;22)) is characteristic of chronic myelogenous leukemia

Evasion of Programmed Cell Death (Apoptosis)

Apoptosis is programmed cell death that occurs in response to pathologic conditions, such as carcinogenic mutations
The Bcl-2 family consists of 25 pro-apoptotic or anti-apoptotic genes.
- Examples: Bcl-2 (anti-apoptotic), Bcl-XL, Bax, BAD, etc.
- The relative expression of these proteins determines cell fate
Certain cancers evade apoptosis by overexpression of Bcl-2
- Example: Follicular lymphoma overexpresses Bcl-2 via a chromosomal translocation (t(14;18))

Lynch Syndrome

Lynch syndrome is most commonly associated with colorectal cancer
It is caused by mutations in mismatch repair (MMR) genes.
MMR genes repair errors in DNA replication
- Cells with MMR deficiencies show microsatellite instability (MSI)
  - Microsatellites are short repetitive DNA sequences that are prone to mutations in MMR deficient cells
  - MSI can affect gene expression and protein function

BRCA and Familial Breast Cancer

10-15% of breast cancers are hereditary.
BRCA1 and BRCA2 are mutated in 25% of familial breast cancer cases.
BRCA proteins participate in homologous recombination repair of DNA breaks.
Cells lacking functional BRCA1/BRCA2 proteins develop chromosomal breaks and aneuploidy (wrong number of chromosomes).
BRCA1/2 mutations can also increase the risk of other cancers, such as ovarian, pancreatic, and prostate cancer.

Driving Carcinogenesis

Neoplasia is a genetic disease.
Carcinogenesis results from the accumulation of mutations in key regulatory genes, leading to uncontrolled cell growth and the development of cancer.
Four main classes of genes are targets of cancer-causing mutations:
- Proto-oncogenes (growth-promoting)
- Tumor suppressor genes (growth-inhibiting)
- Genes that regulate apoptosis
- Genes involved in DNA repair
Carcinogenesis is a stepwise process that occurs due to these mutations overtime

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz covers fundamental concepts of genetics, including gene structure, allele variations, and chromosome information. It also explores the cell cycle, detailing the phases and regulatory proteins involved in cell division. Test your understanding of these essential biological processes!