If DNA is damaged in the cell cycle, which gene causes cell cycle arrest?
Ans. (c) p53Ref: Robbins and Cotran Pathologic Basic Disease 9th Ed; Page No-28P53* Gene in chromosome 17p 13.1* It is called as "genome guardian protein".* Encodes a53Ka protein* p53 is universally expressed in all cells.* p53 induces p21, which inhibits CDKs- hypo-phosphorylation (activation) ofRb- inhibition of G1 -S progression.* It regulates cell cycle progressions, DNA repair, cellular senescence and apoptosis.Note* The suppressor gene p53 apoptosis by depositing CD95 on the cell membrane surface.* Mutations in tumor suppressor genes can result in unrestrained cell division (eg, Li-Fraumeni syndrome).Extra Mile* Mutated p53 protein inactivation promotes tumor development.* Its gene product is broken down more slowly than normal protein, leading to intranuclear accumulation of p53 protein.How to rule out other options?* Rb gene:# Tumor suppressive pocket' protein that binds E2F transcription factors in its hyperphosphorylated state.# It prevents G1/S transition.* RAS oncogene# It is a signal transduction protein.# Most common oncogene mutation involved in human cancer (15-20% of human cancer).# Normal RAS proteins alternate between activated GTP- bound signal transmitting and inactive GDP-bound forms.# When the cells are stimulated by growth factors RAS becomes activated by exchanging GDP to GTP# Activated RAS binds to farnesyl transferase to activate MAP kinase for induction of mitogenesis.# The mutant RAS activates the mitogen-activated protein (MAP) kinase pathway leading to cell proliferation.* MYC# It is most common nuclear transcription factor affected in human tumors.# MYC up regulates expression of telomerase.# It reprogram somatic cell into pluripotent stem cells and contribute to cancer cell "sternness".
Rb
MYC
p53
K-RAS
Neoplasia