Normal cell cycle regulation is a highly coordinated process that ensures cells grow, replicate DNA accurately, repair damage, and divide only when appropriate. It is controlled by signaling proteins, checkpoints, and regulatory molecules that maintain genomic stability and prevent uncontrolled cell growth. Disruption of these regulatory mechanisms can lead to diseases such as cancer.
G₁ Phase The cell increases in size and produces proteins, RNA, and cellular components necessary for DNA replication. Environmental conditions such as nutrients, growth factors, and cellular stress are assessed. Functions: Cell growth Protein synthesis Metabolic activity Preparation for DNA replication Assessment of external signals S Phase DNA replication occurs, ensuring each daughter cell receives a complete set of genetic material. Functions: DNA duplication Histone synthesis Chromosome replication Genetic information preservation G₂ Phase The cell verifies DNA replication accuracy and prepares for mitosis. Functions: DNA damage repair Synthesis of mitotic proteins Cell size assessment Preparation for chromosome separation M Phase Cellular components are equally distributed between daughter cells. Functions: Chromosome segregation Nuclear division Cytoplasmic division Formation of two daughter cells
A. Cyclins Cyclins are regulatory proteins whose concentration changes throughout the cell cycle. They activate cyclin-dependent kinases. Functions: Regulate cell-cycle timing Activate CDKs Control progression through phases Major cyclins:
Checkpoints act as quality-control systems preventing progression if abnormalities are detected. G₁ Checkpoint (Restriction Point) Functions: Determines whether the cell should divide Detects DNA damage Evaluates nutrients and growth factors Prevents abnormal cells from entering S phase Important regulators: p53 p21 Retinoblastoma (Rb) protein S-Phase Checkpoint Functions: Monitors DNA replication Detects replication errors Activates repair pathways Major proteins: ATR Chk1 G₂ Checkpoint Functions: Verifies complete DNA replication Detects DNA damage Delays mitosis if abnormalities exist Major proteins: ATM ATR Chk1 Chk2 M Checkpoint (Spindle Assembly Checkpoint) Functions: Ensures chromosomes attach correctly to spindle fibers Prevents unequal chromosome distribution Major proteins: MAD proteins BUB proteins
p53 Often called the "guardian of the genome." Functions: Detects DNA damage Stops cell cycle progression Activates DNA repair Initiates apoptosis if damage is irreparable Retinoblastoma protein (Rb) Functions: Restrains G₁ to S transition Controls transcription factors Prevents unnecessary cell division p21 Functions: Inhibits CDKs Causes temporary cell cycle arrest Allows DNA repair
