The occurrence of DNA double strand breaks induces cell cycle arrest in mortal and immortal @entity1 cells. In normal, mortal fibroblasts this block to proliferation is permanent. It depends on the growth regulator @entity876 and a protein @entity876 induces, the cyclin dependent kinase inhibitor, @entity994 . We show here that following DNA damage in mortal fibroblasts, the induction of @entity994 and @entity876 is to a large degree shortlived. By 8 days after a brief exposure to DNA strand breaking agents, @entity1732 or @entity4316 , @entity876 protein is at baseline levels, while the @entity876 transactivation level is only slightly above its baseline. By this time the concentration of @entity994 protein, which goes up as high as 100-fold shortly after treatment, is down to just 2-4-fold over baseline levels. Following the drop in @entity994 concentration a large increase in the expression level of the @entity5 suppressor gene @entity986 is observed. This scenario, where a transient increase in @entity994 is followed by a delayed induction of @entity986 , also happens with the permanent arrest that occurs with cellular senescence. In fact, these cells treated with agents that cause DNA double strand breaks share a number of additional markers with senescent cells. Our findings indicate that these cells are very similar to senescent cells and that they have additional factor(s) beside @entity994 and @entity876 that maintain cell cycle arrest.

Agents that cause DNA double strand breaks lead to XXXX enrichment and the premature senescence of normal fibroblasts.

@entity1 :: ('9606', 'Species') :: ['human'] @entity986 :: ('1029', 'Gene') :: ['p16INK4a'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity4316 :: ('MESH:D003609', 'Chemical') :: ['actinomycin D'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity1732 :: ('MESH:D001761', 'Chemical') :: ['bleomycin'] @entity994 :: ('1026', 'Gene') :: ['p21']
@entity986 :: (1029,Gene) :: ['p16INK4a']
