Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints - PubMed (original) (raw)

. 2006 Nov 30;444(7119):633-7.

doi: 10.1038/nature05268.

Nousin Rezaei, Michalis Liontos, Panagiotis Karakaidos, Dimitris Kletsas, Natalia Issaeva, Leandros-Vassilios F Vassiliou, Evangelos Kolettas, Katerina Niforou, Vassilis C Zoumpourlis, Munenori Takaoka, Hiroshi Nakagawa, Frederic Tort, Kasper Fugger, Fredrik Johansson, Maxwell Sehested, Claus L Andersen, Lars Dyrskjot, Torben Ørntoft, Jiri Lukas, Christos Kittas, Thomas Helleday, Thanos D Halazonetis, Jiri Bartek, Vassilis G Gorgoulis

Affiliations

Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints

Jirina Bartkova et al. Nature. 2006.

Abstract

Recent studies have indicated the existence of tumorigenesis barriers that slow or inhibit the progression of preneoplastic lesions to neoplasia. One such barrier involves DNA replication stress, which leads to activation of the DNA damage checkpoint and thereby to apoptosis or cell cycle arrest, whereas a second barrier is mediated by oncogene-induced senescence. The relationship between these two barriers, if any, has not been elucidated. Here we show that oncogene-induced senescence is associated with signs of DNA replication stress, including prematurely terminated DNA replication forks and DNA double-strand breaks. Inhibiting the DNA double-strand break response kinase ataxia telangiectasia mutated (ATM) suppressed the induction of senescence and in a mouse model led to increased tumour size and invasiveness. Analysis of human precancerous lesions further indicated that DNA damage and senescence markers cosegregate closely. Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources