caretaker tumour suppressor genes
Caretaker tumour suppressor genes and genome integrity
In contrast to gatekeeper tumour suppressor genes, caretaker tumour suppressor genes genes do not directly regulate proliferation, but act to prevent genomic instability.
Thus, mutation of caretaker genes leads to accelerated conversion of a normal cell to a neoplastic cell.
Many caretaker genes are required for the maintenance of genome integrity. Caretaker genes play a role, directly or indirectly, in the repair of DNA strand breaks by the homologous recombination pathway, and that are associated with cancer-prone clinical syndromes, in particular ataxia telangiectasia, hereditary breast cancer, Bloom syndrome and Werner syndrome.
ataxia telangiectasia (ATM gene)
hereditary breast cancer (BRCAs: BRCA1 and BRCA2)
mutations of RecQ helicases (RECQLs)
- RECQL2 (MIM.604611): Werner syndrome (MIM.277700)
- RECQL3: Bloom syndrome
- RECQL4 (MIM.603781): Rothmund-Thomson syndrome (MIM.268400) and RAPADILINO syndrome
References
Levitt NC, Hickson ID. Caretaker tumour suppressor genes that defend genome integrity. Trends Mol Med. 2002 Apr;8(4):179-86. PMID: 11927276