Heterochromatin loss as a determinant of progerin-induced DNA damage in Hutchinson-Gilford Progeria.

ABSTRACT: Hutchinson-Gilford progeria is a premature aging syndrome caused by a truncated form of lamin A called progerin. Progerin expression results in a variety of cellular defects including heterochromatin loss, DNA damage, impaired proliferation and premature senescence. It remains unclear how these different progerin-induced phenotypes are temporally and mechanistically linked. To address these questions, we use a doxycycline-inducible system to restrict progerin expression to different stages of the cell cycle. We find that progerin expression leads to rapid and widespread loss of heterochromatin in G1-arrested cells, without causing DNA damage. In contrast, progerin triggers DNA damage exclusively during late stages of DNA replication, when heterochromatin is normally replicated, and prefere

SUBMITTER: Chojnowski A 

PROVIDER: S-EPMC7059134 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature