The DNA Damage Response-Repair or Despair?

被引:36
作者
Ljungman, Mats [1 ,2 ]
机构
[1] Univ Michigan, Dept Radiat Oncol, Ctr Comprehens Canc, Div Radiat & Canc Biol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA
关键词
DNA repair; cell cycle checkpoints; apoptosis; aging; review; cancer; NUCLEOTIDE EXCISION-REPAIR; LIGHT-INDUCED APOPTOSIS; DOUBLE-STRAND BREAKS; MONOCHROMATIC ULTRAVIOLET-RADIATION; TRANSCRIPTION-COUPLED REPAIR; CELL-CYCLE REGULATION; LI-FRAUMENI SYNDROME; RNA-POLYMERASE-II; XERODERMA-PIGMENTOSUM; ESCHERICHIA-COLI;
D O I
10.1002/em.20597
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
The term "the DNA damage response" (DDR) encompasses a sophisticated array of cellular initiatives set in motion as cells are exposed to DNA-damaging events. It has been known for over half a century that all organisms have the ability to restore genomic integrity through DNA repair. More recent discoveries of signal transduction pathways linking DNA damage to cell cycle arrest and apoptosis have greatly expanded our views of how cells and tissues limit mutagenesis and tumorigenesis. DNA repair not only plays a pivotal role in suppressing mutagenesis but also in the reversal of signals inducing the stress response. If repair is faulty or the cell is overwhelmed by damage, chances are that the cell will despair and be removed by apoptosis. This final fate is determined by intricate cellular dosimeters that are yet to be fully understood. Here, key findings leading to our current view of DDR are discussed as well as potential areas of importance for future studies. Environ. Mol. Mutagen. 51:879-889, 2010. (c) 2010 Wiley-Liss, Inc.
引用
收藏
页码:879 / 889
页数:11
相关论文
共 131 条
[1]   Phosphorylation of HuR by Chk2 regulates SIRT1 expression [J].
Abdelmohsen, Kotb ;
Pullmann, Rudolf, Jr. ;
Lai, Ashish ;
Kim, Hyeon Ho ;
Galban, Stefanie ;
Yang, Xiaoling ;
Blethrow, Justin D. ;
Walker, Mark ;
Shubert, Jonathan ;
Gillespie, David A. ;
Furneaux, Henry ;
Gorospe, Myriam .
MOLECULAR CELL, 2007, 25 (04) :543-557
[2]   p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene [J].
Adimoolam, S ;
Ford, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12985-12990
[3]   The N-Terminal Domain of the Drosophila Retinoblastoma Protein Rbf1 Interacts with ORC and Associates with Chromatin in an E2F Independent Manner [J].
Ahlander, Joseph ;
Chen, Xiao-Bo ;
Bosco, Giovanni .
PLOS ONE, 2008, 3 (07)
[4]   ATR kinase is required for global genomic nucleotide excision repair exclusively during S phase in human cells [J].
Auclair, Yannick ;
Rouget, Raphael ;
Affar, El Bachir ;
Drobetsky, Elliot A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (46) :17896-17901
[5]   MCM proteins: DNA damage, mutagenesis and repair [J].
Bailis, JM ;
Forsburg, SL .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2004, 14 (01) :17-21
[6]   DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J].
Bakkenist, CJ ;
Kastan, MB .
NATURE, 2003, 421 (6922) :499-506
[7]   DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis [J].
Bartkova, J ;
Horejsi, Z ;
Koed, K ;
Krämer, A ;
Tort, F ;
Zieger, K ;
Guldberg, P ;
Sehested, M ;
Nesland, JM ;
Lukas, C ;
Orntoft, T ;
Lukas, J ;
Bartek, J .
NATURE, 2005, 434 (7035) :864-870
[8]   Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints [J].
Bartkova, Jirina ;
Rezaei, Nousin ;
Liontos, Michalis ;
Karakaidos, Panagiotis ;
Kletsas, Dimitris ;
Issaeva, Natalia ;
Vassiliou, Leandros-Vassilios F. ;
Kolettas, Evangelos ;
Niforou, Katerina ;
Zoumpourlis, Vassilis C. ;
Takaoka, Munenori ;
Nakagawa, Hiroshi ;
Tort, Frederic ;
Fugger, Kasper ;
Johansson, Fredrik ;
Sehested, Maxwell ;
Andersen, Claus L. ;
Dyrskjot, Lars ;
Orntoft, Torben ;
Lukas, Jiri ;
Kittas, Christos ;
Helleday, Thomas ;
Halazonetis, Thanos D. ;
Bartek, Jiri ;
Gorgoulis, Vassilis G. .
NATURE, 2006, 444 (7119) :633-637
[9]   ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2 [J].
Beucher, Andrea ;
Birraux, Julie ;
Tchouandong, Leopoldine ;
Barton, Olivia ;
Shibata, Atsushi ;
Conrad, Sandro ;
Goodarzi, Aaron A. ;
Krempler, Andrea ;
Jeggo, Penny A. ;
Loebrich, Markus .
EMBO JOURNAL, 2009, 28 (21) :3413-3427
[10]   ISOLATION AND IDENTIFICATION OF THE IRRADIATION PRODUCT OF THYMINE [J].
BEUKERS, R ;
BERENDS, W .
BIOCHIMICA ET BIOPHYSICA ACTA, 1960, 41 (03) :550-551