Genes in context Caretaker gene

1 genes in context

1.1 pathways cancer via caretakers
1.2 pathways cancer via gatekeepers
1.3 pathways cancer via landscapers

genes in context
pathways cancer via caretakers

the process of dna replication inherently places cells @ risk of acquiring mutations. thus, caretaker genes vitally important cellular health. rounds of cell replication allow fixation of mutated genes genome. caretaker genes provide genome stability preventing accumulation of these mutations.

factors contribute genome stabilization include proper cell-cycle checkpoints, dna repair pathways, , other actions ensure cell survival following dna damage. specific dna maintenance operations encoded caretaker genes include nucleotide excision repair, base excision repair, non-homologous end joining recombination pathways, mismatch repair pathways, , telomere metabolism.

upon mutation, caretaker genes lead altered gene products result in increased conversion of normal cell cell of neoplasia, cell that; (1) divides more should or (2) not die when conditions warrant cell death. thus, caretaker genes not directly regulate cell proliferation. in genetic knock-out , rescue experiments, restoration of caretaker gene mutated form wildtype version not limit tumorigenesis. because caretaker genes indirectly contribute pathway cancer.

inactivation of caretaker genes environmentally equivalent exposing cell mutagens incessantly. example, mutation in caretaker gene coding dna repair pathway leads inability repair dna damage allow uncontrolled cell growth. result of mutations of other genes accumulate unchecked result of faulty gene products encoded caretakers.

in addition providing genomic stability, caretakers provide chromosomal stability. chromosomal instability resulting dysfunctional caretaker genes common form of genetic instability leads cancer in humans. in fact, has been proposed these caretaker genes responsible many hereditary predispositions cancers.

in individuals predisposed cancer via mutations in caretaker genes, total of 3 subsequent somatic mutations required acquire cancerous phenotype. mutations must occur in remaining normal caretaker allele in addition both alleles of gatekeeper genes within cell said cell turn neoplasia. thus, risk of cancer in these affected populations less when compared cancer risk in families predisposed cancer via gatekeeper pathway.

pathways cancer via gatekeepers

in many cases, gatekeeper genes encode system of checks , balances monitor cell division , death. when tissue damage occurs, example, products of gatekeeper genes ensure balance of cell growth on cellular death remains in check. in presence of competent gatekeeper genes, mutations of other genes not lead on-going growth imbalances.

mutations altering these genes lead irregular growth regulation , differentiation. each cell type has one, or @ least few, gatekeeper genes. if person predisposed cancer, have inherited mutation in 1 of 2 copies of gatekeeper gene. mutation of alternate allele leads progression neoplasia.

historically, term gatekeeper gene first coined in association apc gene, tumor suppressor consistently found mutated in colorectal tumors. gatekeeper genes in fact specific tissues in reside.

the probability mutations occur in other genes increases when dna repair pathway mechanisms damaged result of mutations in caretaker genes. thus, probability mutation take place in gatekeeper gene increases when caretaker gene has been mutated.

apoptosis, or induced cell suicide, serves mechanism prevent excessive cellular growth. gatekeeper genes regulate apoptosis. however, in instances tissue growth or regrowth warranted, these signals must inactivated or net tissue regeneration impossible. thus, mutations in growth-controlling genes lead characteristics of uncontrolled cellular proliferation, neoplasia, while in parallel cell had no mutations in gatekeeper function, simple cell death ensue.

pathways cancer via landscapers

a third group of genes in mutations lead significant susceptibility cancer class of landscaper genes. products encoded landscaper genes not directly affect cellular growth, when mutated, contribute neoplastic growth of cells fostering stromal environments conducive unregulated cell proliferation.

landscaper genes encode gene products control microenvironment in cells grow. growth of cells depends both on cell-to-cell interactions , cell-to-extracellular matrix (ecm) interactions. mechanisms of control via regulation of extracellular matrix proteins, cellular surface markers, cellular adhesion molecules, , growth factors have been proposed.

cells communicate each other via ecm through both direct contact , through signaling molecules. stromal cell abnormalities arising gene products coded faulty landscaper genes induce abnormal cell growth on epithelium, leading cancer of tissue.

biochemical cascades consisting of signaling proteins occur in ecm , play important role regulation of many aspects of cell life. landscaper genes encode products determine composition of membranes in cells live. example, large molecular weight glycoproteins , proteoglycans have been found in association signaling , structural roles. there exist proteolytic molecules in ecm essential clearing unwanted molecules, such growth factors, cell adhesion molecules, , others space surrounding cells. proposed landscaper genes control mechanisms these factors cleared. different characteristics of these membranes lead different cellular effects, such differing rates of cell proliferation or differentiation. if, example, ecm disrupted, incoming cells, such of immune system, can overload area , release chemical signals induce abnormal cell proliferation. these conditions lead environment conducive tumor growth , cancerous phenotype.