Featured News from the Lab
Joint Department Colloquium starts off the year
We started into 2018 with our third DMMD Colloquium, a day full of scientific talks and poster sessions to foster discussions and provide an overview of our research activities to newcomers. Special feature this time: an entertaining lecture by communication trainer Dani Nieth.
News & Views: Daughters sense their mother's stress
Read the News & Views article on our recently published work on the effects of DNA damage propagation from one cell generation to the next. It nicely puts our work into context with recent findings from the labs of Tobias Meyer, Sabrina Spencer, and Chris Bakal. Access the News & Views via PubMed or the Cell Cycle homepage.
Aleksandra's paper is out
Aleksandra's work shows how inherited DNA lesions, which originate from replication problems during the previous S-phase, determine G1 duration in daughter cells. Her findings provide a deterministic explanation for cellular heterogeneity in cell cycle commitment and further suggest that mild replication stress during cancer development, induced for instance by oncogene activation, cooperates with loss of tumor suppressor protein p53 to force cells into a "vicious cycle" of damage propagation and accumulation of mutations.
Replication stress is a major source of DNA damage and an important driver of cancer development. Replication intermediates that occur upon mild forms of replication stress frequently escape cell cycle checkpoints and can be transmitted through mitosis into the next cell cycle. The consequences of such inherited DNA lesions for cell fate and survival are poorly understood. By using time-lapse microscopy and quantitative image-based cytometry to simultaneously monitor inherited DNA lesions marked by the genome caretaker protein 53BP1 and cell cycle progression, we show that inheritance of 53BP1-marked lesions from the previous S-phase is associated with a prolonged G1 duration in the next cell cycle. These results suggest that cell-to-cell variation in S-phase commitment is determined, at least partially, by the amount of replication-born inherited DNA damage in individual cells. We further show that loss of the tumor suppressor protein p53 overrides replication stress-induced G1 prolongation and allows S-phase entry with excessive amounts of inherited DNA lesions. Thus, replication stress and p53 loss may synergize during cancer development by promoting cell cycle re-entry with unrepaired mutagenic DNA lesions originating from the previous cell cycle.
Link to PubMed:
Lezaja A, Altmeyer M
Cell Cycle. 2017 Oct 5:0. doi: 10.1080/15384101.2017.1383578.