Caretaker gene

Changes in the genome that allow uncontrolled cell proliferation or cell immortality are responsible for cancer. It is believed that the major changes in the genome that lead to cancer arise from mutations in tumor suppressor genes. In 1997, Kinzler and Bert Vogelstein grouped these cancer susceptibility genes into two classes: "caretakers" and "gatekeepers". In 2004, a third classification of tumor suppressor genes was proposed by Franziska Michor, Yoh Iwasa, and Martin Nowak; "landscaper" genes.

Caretaker genes encode products that stabilize the genome. Fundamentally, mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising from improper rearrangement of chromosomes.

In contrast to caretaker genes, gatekeeper genes encode gene products that act to prevent growth of potential cancer cells and prevent accumulation of mutations that directly lead to increased cellular proliferation.

The third classification of genes, the landscapers, encode products that, when mutated, contribute to the neoplastic growth of cells by fostering a stromal environment conducive to unregulated cell proliferation.

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.

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