Genetics and Cell Cycle Overview

Genetics

• A gene is a distinct DNA sequence within a chromosome that acts as instructions for creating proteins.
• Humans have 20,000-25,000 genes, each with two copies – one from each parent.
• Alleles are variations of a single gene that contribute to an individual’s unique physical features.
• A chromosome is a condensed packaging of DNA, with most human cells containing 46 chromosomes in 23 pairs.
• DNA is comprised of four chemical bases (adenine, thymine, guanine, cytosine) arranged in a specific sequence that determines protein structure.
• A chromatid is one of two identical copies of DNA within a chromosome during cell division.

Cell Cycle

• The cell cycle is a series of events that allow a cell to prepare for division and eventually divide into two daughter cells.
• The cell cycle includes the G0 (resting) phase, where the cell spends most of its time, and the active cell division phases.
• Cyclins are proteins that activate cyclin-dependent kinases (CDKs), which drive progression through the cell cycle.
• CDK inhibitors inhibit CDK function and help to regulate the cell cycle.

Neoplasia and Genetics

• Neoplasia is a genetic disease, caused by mutations in four classes of normal regulatory genes:
  • Proto-oncogenes
  • Tumor suppressor genes
  • Apoptosis-regulating genes
  • DNA repair genes

Proto-oncogenes

• Proto-oncogenes are normal genes that promote cell growth.
• Oncogenes are mutated proto-oncogenes that contribute to autonomous cell growth in cancer cells.
• Oncoproteins are the mutant proteins encoded by oncogenes that promote uncontrolled cell growth.
• The MAPK pathway, which is involved in cell signaling, is often altered in ameloblastomas, with BRAF mutations being the most common.
• The BRAFV600E mutation, which occurs in 90% of BRAF mutations in neoplasia, results in a gain-of-function mutation in the BRAF protein, leading to uncontrolled activation of the MAPK pathway.

Evasion of Apoptosis

• Apoptosis is programmed cell death that eliminates cells with damaged or abnormal DNA.
• The Bcl-2 family of proteins, which includes both pro- and anti-apoptotic members, regulates apoptosis.
• Follicular lymphoma can evade apoptosis by overexpressing Bcl-2 through chromosomal translocation, a process where a segment of one chromosome moves to a different chromosome.

Chromosomal Translocations

• Chromosomal translocations are often caused by errors in DNA double-strand break repair.
• The Philadelphia chromosome, a characteristic translocation in chronic myelogenous leukemia, is an example of a translocation that can contribute to cancer development.
• Translocations can also involve the fusion of two genes, as seen in mucoepidermoid carcinoma of the hard palate with the CRTC1-MAML2 translocation.

Mechanisms of Genetic Damage

• Common mechanisms of genetic damage include:
  • Point mutations: single nucleotide changes.
  • Gene deletions: loss of a segment of DNA.
  • Gene amplifications: duplications of a segment of DNA.
  • Chromosomal translocations: exchanges or attachments of chromosomal segments.

Lynch Syndrome

• Lynch syndrome, a hereditary cancer syndrome, is associated with a high risk of colorectal cancer.
• Lynch syndrome involves a dysfunction in the mismatch repair (MMR) system, which is responsible for correcting errors in DNA replication.
• Colorectal cancer in Lynch syndrome is often characterized by microsatellite instability, which occurs when the MMR system is deficient and results in increased mutation rates in repetitive DNA sequences.

BRCA1/BRCA2 and Familial Breast Cancer

• Hereditary mutations in BRCA1 and BRCA2 genes are common in familial breast cancer.
• BRCA1 and BRCA2 are involved in DNA repair, specifically homologous recombination, which uses a sister chromatid as a template to repair DNA breaks during replication.
• Cells lacking functional BRCA1 and BRCA2 are prone to chromosomal breaks and aneuploidy (abnormal chromosome number).

Carcinogenesis

• Carcinogenesis is a multi-step process that involves the accumulation of multiple genetic mutations over time.
• These mutations can occur in proto-oncogenes, tumor suppressor genes, apoptosis-regulating genes, and DNA repair genes.
• The combination of these mutations leads to uncontrolled cell growth, evasion of apoptosis, and tumor development.

Explore the fundamental concepts of genetics and the cell cycle in this informative quiz. Learn about DNA, genes, chromosomes, and the stages of cell division. This quiz will test your understanding of the basic biological processes that govern life.