text: The process of DNA replication inherently places cells at risk of acquiring mutations.  Thus, caretaker genes are vitally important to cellular health.  Rounds of cell replication allow fixation of mutated genes into the genome. Caretaker genes provide genome stability by preventing the accumulation of these mutations.
  Factors that contribute to genome stabilization include proper cell-cycle checkpoints, DNA repair pathways, and other actions that ensure cell survival following DNA damage.  Specific DNA maintenance operations encoded by caretaker genes include nucleotide excision repair, base excision repair, non-homologous end joining recombination pathways, mismatch repair pathways, and telomere metabolism.
  Loss of function mutations in caretaker genes allow mutations in other genes to survive that can result in increased conversion of a normal cell to a neoplastic cell, a cell that; (1) divides more often than it should or (2) does not die when conditions warrant cell death.  Thus, caretaker genes do not directly regulate cell proliferation.  Instead, they prevent other mutations from surviving for example by slowing the cell division process to enable DNA repair to complete, or by initiating apoptosis of the cell.  In genetic knock-out and rescue experiments, restoration of a caretaker gene from the mutated form to the wildtype version does not limit tumorigenesis.  This is because caretaker genes only indirectly contribute to the pathway to cancer.
  Cells deficient in a DNA repair process tend to accumulate unrepaired DNA damages.  Cells defective in apoptosis tend to survive even with excessive DNA damage, thus permitting replication of the damaged DNA and consequently carcinogenic mutations.  Some key caretaker proteins that contribute to cell survival by acting in DNA repair processes when the level of damage is manageable, become executioners by inducing apoptosis when there is excess DNA damage.
  Inactivation of caretaker genes is environmentally equivalent to exposing the cell to mutagens incessantly.  For example, a mutation in a caretaker gene coding for a DNA repair pathway that leads to the inability to properly repair DNA damage could allow uncontrolled cell growth.  This is the result of mutations of other genes that accumulate unchecked as a result of faulty gene products encoded by the caretakers.
  In addition to providing genomic stability, caretakers also provide chromosomal stability.  Chromosomal instability resulting from dysfunctional caretaker genes is the most common form of genetic instability that leads to cancer in humans.  In fact, it has been proposed that these caretaker genes are responsible for many hereditary predispositions to cancers.
  In individuals predisposed to cancer via mutations in caretaker genes, a total of three subsequent somatic mutations are required to acquire the cancerous phenotype.  Mutations must occur in the remaining normal caretaker allele in addition to both alleles of gatekeeper genes within that cell for the said cell to turn to neoplasia.  Thus, the risk of cancer in these affected populations is much less when compared to cancer risk in families predisposed to cancer via the gatekeeper pathway.