Autophagy in DNA Damage Response
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 sugge...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/16/2/2641 |
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| author | Piotr Czarny Elzbieta Pawlowska Jolanta Bialkowska-Warzecha Kai Kaarniranta Janusz Blasiak |
| author_facet | Piotr Czarny Elzbieta Pawlowska Jolanta Bialkowska-Warzecha Kai Kaarniranta Janusz Blasiak |
| author_sort | Piotr Czarny |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:01:54Z |
| format | Article |
| id | doaj.art-1236ab65d4c2420caeb69596ee99dc40 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T15:01:54Z |
| publishDate | 2015-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1236ab65d4c2420caeb69596ee99dc402022-12-22T02:42:15ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-01-011622641266210.3390/ijms16022641ijms16022641Autophagy in DNA Damage ResponsePiotr Czarny0Elzbieta Pawlowska1Jolanta Bialkowska-Warzecha2Kai Kaarniranta3Janusz Blasiak4Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, PolandDepartment of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, PolandDepartment of Infectious and Liver Diseases, Medical University of Lodz, Kniaziewicza 1/5, 92-347 Lodz, PolandDepartment of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio FI-70211, FinlandDepartment of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, PolandDNA 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.http://www.mdpi.com/1422-0067/16/2/2641autophagyDNA damage responseDNA repairapoptosissignal transductionsenescencecancer therapy |
| spellingShingle | Piotr Czarny Elzbieta Pawlowska Jolanta Bialkowska-Warzecha Kai Kaarniranta Janusz Blasiak Autophagy in DNA Damage Response International Journal of Molecular Sciences autophagy DNA damage response DNA repair apoptosis signal transduction senescence cancer therapy |
| title | Autophagy in DNA Damage Response |
| title_full | Autophagy in DNA Damage Response |
| title_fullStr | Autophagy in DNA Damage Response |
| title_full_unstemmed | Autophagy in DNA Damage Response |
| title_short | Autophagy in DNA Damage Response |
| title_sort | autophagy in dna damage response |
| topic | autophagy DNA damage response DNA repair apoptosis signal transduction senescence cancer therapy |
| url | http://www.mdpi.com/1422-0067/16/2/2641 |
| work_keys_str_mv | AT piotrczarny autophagyindnadamageresponse AT elzbietapawlowska autophagyindnadamageresponse AT jolantabialkowskawarzecha autophagyindnadamageresponse AT kaikaarniranta autophagyindnadamageresponse AT januszblasiak autophagyindnadamageresponse |