PMID- 30835165
OWN - NLM
STAT- MEDLINE
DCOM- 20190607
LR  - 20210629
IS  - 1938-5404 (Electronic)
IS  - 0033-7587 (Print)
IS  - 0033-7587 (Linking)
VI  - 191
IP  - 5
DP  - 2019 May
TI  - Sirt2 Regulates Radiation-Induced Injury.
PG  - 398-412
LID - 10.1667/RR15282.1 [doi]
AB  - Sirtuin 2 (SIRT2) plays a major role in aging, carcinogenesis and 
      neurodegeneration. While it has been shown that SIRT2 is a mediator of 
      stress-induced cell death, the mechanism remains unclear. In this study, we 
      report the role of SIRT2 in mediating radiation-induced cell death and DNA damage 
      using mouse embryonic fibroblasts (MEFs), progenitor cells and tissues from Sirt2 
      wild-type and genomic knockout mice, and human tumor and primary cell lines as 
      models. The presence of Sirt2 in cells and tissues significantly enhanced the 
      cell's sensitivity to radiation-induced cytotoxicity by delaying the dispersion 
      of radiation-induced gamma-H2AX and 53BP1 foci. This enhanced cellular 
      radiosensitivity correlated with reduced expression of pro-survival and DNA 
      repair proteins, and decreased DNA repair capacities involving both homologous 
      repair and non-homologous end joining DNA repair mechanisms compared to those in 
      Sirt2 knockout (KO) and knockdown (KD) phenotypes. Together, these data suggest 
      SIRT2 plays a critical role in mediating the radiation-induced DNA damage 
      response, thus regulating radiation-induced cell death and survival.
FAU - Nguyen, Phuongmai
AU  - Nguyen P
AD  - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Shukla, Sudhanshu
AU  - Shukla S
AD  - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Liu, Ryan
AU  - Liu R
AD  - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Abbineni, Gopal
AU  - Abbineni G
AD  - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
FAU - Smart, DeeDee K
AU  - Smart DK
AD  - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health, Bethesda, Maryland.
LA  - eng
GR  - Z99 CA999999/ImNIH/Intramural NIH HHS/United States
GR  - ZIA BC011222/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20190305
PL  - United States
TA  - Radiat Res
JT  - Radiation research
JID - 0401245
RN  - EC 3.5.1.- (Sirtuin 2)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Survival/radiation effects
MH  - Cognition/radiation effects
MH  - DNA Damage
MH  - Fibroblasts/radiation effects
MH  - Homologous Recombination/radiation effects
MH  - Mice
MH  - Radiation Injuries, Experimental/genetics/*metabolism/pathology/physiopathology
MH  - Radiation Tolerance
MH  - Sirtuin 2/*metabolism
PMC - PMC8237344
MID - NIHMS1029667
EDAT- 2019/03/06 06:00
MHDA- 2019/06/08 06:00
PMCR- 2021/06/28
CRDT- 2019/03/06 06:00
PHST- 2019/03/06 06:00 [pubmed]
PHST- 2019/06/08 06:00 [medline]
PHST- 2019/03/06 06:00 [entrez]
PHST- 2021/06/28 00:00 [pmc-release]
AID - 10.1667/RR15282.1 [pii]
AID - 10.1667/RR15282.1 [doi]
PST - ppublish
SO  - Radiat Res. 2019 May;191(5):398-412. doi: 10.1667/RR15282.1. Epub 2019 Mar 5.