细胞衰老_课件.pptVIP

Latin A–Dependent NuclearDefects in Human Aging Paola Scaffidi and Tom Misteli* SCIENCE VOL 312 19 MAY 2006 Contents 1、 About HGPS HGPS was first described in 1886 by Jonathan Hutchinson and also described independently in 1897 by Hasting Gilford. Mutations in the nuclear structural protein lamin A cause HGPS. About HGPS HGPS patient cells have various defects in nuclear structure and function： 1）、dysmorphic nuclear shape 2）、increased DNA damage 3）、down-regulation of several nuclear proteins, including the HP1 and the LAP2 group of lamin A–associated proteins 4）、altered histone modification patterns ，including reduced heterochromatinspecific trimethylation of Lys9 on histone H3 (Tri-Me-K9H3) 2、 HGPS-like nuclear defects Whether lamin A plays any role in normal aging is unknown. To address these questions, we determined whether HGPS-like nuclear defects occurred in cells from normally aged individuals. fluorescent signal 1 fluorescent signal 1 第一个结论 We conclude that cells from HGPS patients and normally aged individuals share several common nuclear defects. 3、sporadic use of the cryptic splice site in lamin A 1、 whether the cryptic solic site ,whose constitutive activation causes HGPS, is also used by default in cells from healthy individuals. 2 3、sporadic use of the cryptic splice site in lamin A 2、 the cryptic splice site in the wild-type LMNA gene is highly homologous to a generic consensus splice donor site (Fig. 2A). 3、Reverse transcription polymerase chain reaction (RTPCR) using primers in exon 9 and 12 amplified a minor truncated product in cells from healthy individuals of all ages (Fig. 2, B and C). 3、sporadic use of the cryptic splice site in lamin A all cell lines tested expressed the D150 LMNA isoform when detected with a pair of primers specific for the aberrant splice junction (Fig. 2, B and D). Transfection of a splicing reporter in multiple cell lines from both y