SMG1 heterozygosity exacerbates haematopoietic cancer development in Atm null mice by increasing persistent DNA damage and oxidative stress.

ABSTRACT: Suppressor of morphogenesis in genitalia 1 (SMG1) and ataxia telangiectasia mutated (ATM) are members of the PI3-kinase like-kinase (PIKK) family of proteins. ATM is a well-established tumour suppressor. Loss of one or both alleles of ATM results in an increased risk of cancer development, particularly haematopoietic cancer and breast cancer in both humans and mouse models. In mice, total loss of SMG1 is embryonic lethal and loss of a single allele results in an increased rate of cancer development, particularly haematopoietic cancers and lung cancer. In this study, we generated mice deficient in Atm and lacking one allele of Smg1, Atm^-/- Smg1^gt/+ mice. These mice developed cancers more rapidly than either of the parental genotypes, and all cancers were haematopoietic

SUBMITTER: Ho U 

PROVIDER: S-EPMC6850945 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature