Diseases of DNA repair

Stable Identifier
Homo sapiens
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Inherited and sporadic defects in genes that encode proteins that participate in DNA repair give rise to genetic instability that can lead to malignant transformation or trigger cellular senescence or apoptosis. Inherited defects in DNA repair genes are the underlying cause of familial cancer syndromes and premature ageing syndromes. Sporadic defects in DNA repair genes are frequently found in tumors. For review, please refer to Tiwari and Wilson 2019.

We have so far annotated diseases of mismatch repair and diseases of base excision repair.

Defects in mammalian DNA mismatch repair (MMR) genes (MLH1, PMS2, MSH2, and MSH6) result in microsatellite instability (MSI) and reduced fidelity during replication and repair steps. Defective variants of MMR genes are associated with sporadic cancers with hypermutation phenotype as well as hereditary cancer syndromes such as Lynch syndrome (hereditary non-polyposis colorectal cancer) and constitutional mismatch repair deficiency syndrome (CMMRD). MSI is an important predictor of sensitivity to cancer immunotherapy. For review, please refer to Pena-Diaz and Rasmussen 2016, Sijmons and Hofstra 2016, Tabori et al. 2017, Baretti and Le 2018.
Germline mutations, single nucleotide polymorphisms (SNPs) and somatic mutations in several genes involved in base excision repair (BER), a DNA repair pathway where a damaged DNA base is excised and replaced with a correct base, are involved in the development of cancer and several oxidative stress-related diseases. For review, please refer to Fu et al. 2012, Fletcher and Houlston 2010, Brenerman et al. 2014, Patrono et al. 2014, and D'Errico et al. 2017.

Literature References
PubMed ID Title Journal Year
26708048 Approaches to diagnose DNA mismatch repair gene defects in cancer

Peña-Diaz, J, Rasmussen, LJ

DNA Repair (Amst.) 2016
25355293 Base excision repair capacity in informing healthspan

Brenerman, BM, Illuzzi, JL, Wilson, DM

Carcinogenesis 2014
25493225 Polymorphisms in base excision repair genes: Breast cancer risk and individual radiosensitivity

Patrono, C, Sterpone, S, Testa, A, Cozzi, R

World J Clin Oncol 2014
28572265 Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood

Tabori, U, Hansford, JR, Achatz, MI, Kratz, CP, Plon, SE, Frebourg, T, Brugières, L

Clin. Cancer Res. 2017
20414203 Architecture of inherited susceptibility to common cancer

Fletcher, O, Houlston, RS

Nat. Rev. Cancer 2010
26746812 Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

Sijmons, RH, Hofstra, RMW

DNA Repair (Amst.) 2016
31374202 DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging

Tiwari, V, Wilson, DM

Am. J. Hum. Genet. 2019
27932076 Single nucleotide polymorphisms in DNA glycosylases: From function to disease

D'Errico, M, Parlanti, E, Pascucci, B, Fortini, P, Baccarini, S, Simonelli, V, Dogliotti, E

Free Radic. Biol. Med. 2017
22237395 Balancing repair and tolerance of DNA damage caused by alkylating agents

Fu, D, Calvo, JA, Samson, LD

Nat. Rev. Cancer 2012
29669262 DNA mismatch repair in cancer

Baretti, M, Le, DT

Pharmacol. Ther. 2018
Participant Of
Name Identifier Synonyms
genetic disease 630
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