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Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place
Ist Teil von
Cancer discovery, 2018-05, Vol.8 (5), p.537-555
Ort / Verlag
United States
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
Oncogene activation disturbs cellular processes and accommodates a complex landscape of changes in the genome that contribute to genomic instability, which accelerates mutation rates and promotes tumorigenesis. Part of this cellular turmoil involves deregulation of physiologic DNA replication, widely described as replication stress. Oncogene-induced replication stress is an early driver of genomic instability and is attributed to a plethora of factors, most notably aberrant origin firing, replication-transcription collisions, reactive oxygen species, and defective nucleotide metabolism.
Replication stress is a fundamental step and an early driver of tumorigenesis and has been associated with many activated oncogenes. Deciphering the mechanisms that contribute to the replication stress response may provide new avenues for targeted cancer treatment. In this review, we discuss the latest findings on the DNA replication stress response and examine the various mechanisms through which activated oncogenes induce replication stress.