Constricted migration increases DNA damage and independently represses cell cycle.

ABSTRACT: Cell migration through dense tissues or small capillaries can elongate the nucleus and even damage it, and any impact on cell cycle has the potential to affect various processes including carcinogenesis. Here, nuclear rupture and DNA damage increase with constricted migration in different phases of cell cycle-which we show is partially repressed. We study several cancer lines that are contact inhibited or not and that exhibit diverse frequencies of nuclear lamina rupture after migration through small pores. DNA repair factors invariably mislocalize after migration, and an excess of DNA damage is evident as pan--nucleoplasmic foci of phosphoactivated ATM and γH2AX. Foci counts are suppressed in late cell cycle as expected of mitotic checkpoints, and migration of contact-inhibited cells thro

SUBMITTER: Pfeifer CR 

PROVIDER: S-EPMC6232975 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature