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Cellular survival over genomic perfection

Accepted version
Peer-reviewed

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Type

Article

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Authors

Hall, Benjamin A 

Abstract

Damage to DNA occurs continuously. DNA quality control mechanisms, such as DNA repair and replicative pathways, mitigate that damage and preserve the DNA sequence. Mutations are believed to arise when DNA lesions are not repaired appropriately, and they are thought to be an indicator of ineffectual DNA quality control. Yet, DNA sequencing of normal tissues reveals that considerable somatic mutagenesis is common. Mutagenesis appears to be the inevitable outcome of cellular wear and tear and is not necessarily cancer associated. Perhaps mutagenesis is not due to failings of DNA quality control mechanisms. Rather, such pathways may be naturally limited in activity, resulting in permissiveness to mutagenesis. We suggest that this is a prioritization of survival over genomic perfection, given that most DNA damage is inconsequential and thus, affordable.

Description

Keywords

Carcinogenesis, Cell Survival, Class I Phosphatidylinositol 3-Kinases, DNA Damage, DNA Repair, Genomics, Humans, Mutagenesis, Neoplasms, Receptor, Notch1

Journal Title

Science

Conference Name

Journal ISSN

2048-7754
1095-9203

Volume Title

366

Publisher

American Association for the Advancement of Science
Sponsorship
Cancer Research UK (23916)
Dr. Josef Steiner Cancer Foundation (Award 2019)
Medical Research Council (MC_UU_12022/9)
B.A.H. is supported by the Royal Society (grant no. UF130039). S.N.-Z. is supported by a Cancer Research UK (CRUK) Advanced Clinician Scientist Award (C60100/A23916) and the Josef Steiner Foundation. Both authors are supported by a Medical Research Council (MRC) Grant-in-Aid to the MRC Cancer unit.