Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage
2006
. The relationshipbetween these two barriers, if any, has not been elucidated. Herewe show that oncogene-induced senescence is associated withsignsofDNAreplicationstress,includingprematurelyterminatedDNAreplicationforksandDNAdouble-strand breaks.Inhibitingthe DNA double-strand break response kinase ataxia telangiecta-siamutated(ATM)suppressedtheinductionofsenescenceandina mouse model led to increased tumour size and invasiveness.Analysis of human precancerous lesions further indicated thatDNA damage and senescence markers cosegregate closely. Thus,senescence in human preneoplastic lesions is a manifestation ofoncogene-induced DNA replication stress and, together withapoptosis, provides a barrier to malignant progression.There are several forms of senescence. Replicative senescence, theform induced by eroded telomeres, depends on activation of theDNA double-strand break (DSB) checkpoint kinases ATM andcheckpointkinase2(Chk2)
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