Autophagy in DNA Damage Response

International Journal of Molecular Sciences

Piotr Czarny¹  Elzbieta Pawlowska²  Jolanta Bialkowska-Warzecha⁴  Kai Kaarniranta³  Janusz Blasiak¹ 

[1] Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; E-Mail:;Department of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland; E-Mail:;Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio FI-70211, Finland; E-Mail:;Department of Infectious and Liver Diseases, Medical University of Lodz, Kniaziewicza 1/5, 92-347 Lodz, Poland; E-Mail:

关键词: autophagy;    DNA damage response;    DNA repair;    apoptosis;    signal transduction;    senescence;    cancer therapy;   

DOI  :  10.3390/ijms16022641

来源: mdpi

【 摘 要 】

DNA damage response (DDR) involves DNA repair, cell cycle regulation and apoptosis, but autophagy is also suggested to play a role in DDR. Autophagy can be activated in response to DNA-damaging agents, but the exact mechanism underlying this activation is not fully understood, although it is suggested that it involves the inhibition of mammalian target of rapamycin complex 1 (mTORC1). mTORC1 represses autophagy via phosphorylation of the ULK1/2–Atg13–FIP200 complex thus preventing maturation of pre-autophagosomal structures. When DNA damage occurs, it is recognized by some proteins or their complexes, such as poly(ADP)ribose polymerase 1 (PARP-1), Mre11–Rad50–Nbs1 (MRN) complex or FOXO3, which activate repressors of mTORC1. SQSTM1/p62 is one of the proteins whose levels are regulated via autophagic degradation. Inhibition of autophagy by knockout of FIP200 results in upregulation of SQSTM1/p62, enhanced DNA damage and less efficient damage repair. Mitophagy, one form of autophagy involved in the selective degradation of mitochondria, may also play role in DDR. It degrades abnormal mitochondria and can either repress or activate apoptosis, but the exact mechanism remains unknown. There is a need to clarify the role of autophagy in DDR, as this process may possess several important biomedical applications, involving also cancer therapy.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.