Asset Details
Do you wish to reserve the book?
Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells
Do you wish to request the book?
Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells
2016
Overview
The main characteristic of senescence is its stability which relies on the persistence of DNA damage. We show that unlike fibroblasts, senescent epithelial cells do not activate an ATM-or ATR-dependent DNA damage response (DDR), but accumulate oxidative-stress-induced DNA single-strand breaks (SSBs). These breaks remain unrepaired because of a decrease in PARP1 expression and activity. This leads to the formation of abnormally large and persistent XRCC1 foci that engage a signalling cascade involving the p38MAPK and leading to p16 upregulation and cell cycle arrest. Importantly, the default in SSB repair also leads to the emergence of post-senescent transformed and mutated precancerous cells. In human-aged skin, XRCC1 foci accumulate in the epidermal cells in correlation with a decline of PARP1, whereas DDR foci accumulate mainly in dermal fibroblasts. These findings point SSBs as a DNA damage encountered by epithelial cells with aging which could fuel the very first steps of carcinogenesis.
It is recognized that cellular senescence is triggered by DNA damage as a protective mechanism against tumorigenesis. Here the authors show that DNA single-strand breaks of oxidative origin can induce a transient senescent state followed by the emergence of clonal transformed cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/31
/ 13/51
/ 13/89
/ 14
/ 14/19
/ 14/32
/ Cancer
/ DNA
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Epithelial Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Poly (ADP-Ribose) Polymerase-1
/ Poly(ADP-ribose) Polymerases - genetics
/ Poly(ADP-ribose) Polymerases - metabolism
/ Science
/ Tumors
