Oncofetal HMGA2 attenuates genotoxic damage induced by topoisomerase II target compounds through the regulation of local DNA topology.

ABSTRACT: Rapidly dividing cells maintain chromatin supercoiling homeostasis via two specialized classes of enzymes, DNA topoisomerase type 1 and 2 (TOP1/2). Several important anticancer drugs perturb this homeostasis by targeting TOP1/2, thereby generating genotoxic DNA damage. Our recent studies indicated that the oncofetal chromatin structuring high-mobility group AT-hook 2 (HMGA2) protein plays an important role as a DNA replication fork chaperone in coping with DNA topological ramifications that occur during replication stress, both genomewide and at fragile sites such as subtelomeres. Intriguingly, a recent large-scale clinical study identified HMGA2 expression as a sole predicting marker for relapse and poor clinical outcomes in 350 acute myeloid leukemia (AML) patients receiving combinatoria

SUBMITTER: Ahmed SM 

PROVIDER: S-EPMC6763970 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature