PMID- 33573186
OWN - NLM
STAT- MEDLINE
DCOM- 20210722
LR  - 20210722
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 12
IP  - 2
DP  - 2021 Jan 30
TI  - Ablation of SMUG1 Reduces Cell Viability and Increases UVC-Mediated Apoptosis in 
      Hepatocarcinoma HepG2 Cells.
LID - 10.3390/genes12020201 [doi]
LID - 201
AB  - Uracil is an unavoidable aberrant base in DNA sequences, the repair of which 
      takes place by a highly efficient base excision repair mechanism. The removal of 
      uracil from the genome requires multiple biochemical steps with conformational 
      changes of DNA that inhibit DNA replication and interfere with transcription. 
      However, the relevance of uracil in DNA for cellular physiology and 
      transcriptional regulation is not fully understood. We investigated the 
      functional roles of SMUG1 using knock-down (KD) and knock-out (KO) models. The 
      proliferation ratio of SMUG1 KD and KO cells was decreased compared to WT control 
      cells, and the cell cycle was arrested in the G2/M phases before the transition 
      to mitosis. The apoptotic cell death was increased in KD and KO cell lines 
      through the increase of BAX and active caspase 3 expression. Phospho-gamma-H2AX 
      expression, which reflected accumulated DNA damage, was also increased in KO 
      cells. Moreover, the apoptotic cells by DNA damage accumulation were markedly 
      increased in SMUG1 KD and KO cells after ultraviolet C irradiation. 
      Transcriptomic analysis using RNA-seq revealed that SMUG1 was involved in gene 
      sets expression including cell cycle transition and chromatin silencing. 
      Together, the results implicate SMUG1 as a critical factor in cell cycle and 
      transcriptional regulation.
FAU - An, Mi-Jin
AU  - An MJ
AUID- ORCID: 0000-0002-7588-6243
AD  - Department of Life Science, Chung-Ang University, Seoul 06974, Korea.
FAU - Shin, Geun-Seup
AU  - Shin GS
AD  - Department of Life Science, Chung-Ang University, Seoul 06974, Korea.
FAU - Lee, Hyun-Min
AU  - Lee HM
AUID- ORCID: 0000-0002-7970-2050
AD  - Department of Life Science, Chung-Ang University, Seoul 06974, Korea.
FAU - Kim, Jung-Woong
AU  - Kim JW
AD  - Department of Life Science, Chung-Ang University, Seoul 06974, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210130
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 56HH86ZVCT (Uracil)
RN  - EC 3.2.2.- (SMUG1 protein, human)
RN  - EC 3.2.2.- (Uracil-DNA Glycosidase)
SB  - IM
MH  - Apoptosis/genetics
MH  - Carcinoma, Hepatocellular/*genetics/pathology
MH  - Cell Proliferation/genetics
MH  - Cell Survival/genetics
MH  - DNA Damage
MH  - DNA Repair/genetics
MH  - DNA Replication/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Gene Knockout Techniques
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/*genetics/pathology
MH  - Uracil/*metabolism
MH  - Uracil-DNA Glycosidase/antagonists & inhibitors/*genetics
PMC - PMC7911780
OTO - NOTNLM
OT  - DNA damage repair
OT  - RNA-seq
OT  - SMUG1
OT  - knock-out
OT  - proliferation
COIS- The authors declare no conflict of interest.
EDAT- 2021/02/13 06:00
MHDA- 2021/07/23 06:00
PMCR- 2021/01/30
CRDT- 2021/02/12 01:03
PHST- 2020/12/26 00:00 [received]
PHST- 2021/01/16 00:00 [revised]
PHST- 2021/01/28 00:00 [accepted]
PHST- 2021/02/12 01:03 [entrez]
PHST- 2021/02/13 06:00 [pubmed]
PHST- 2021/07/23 06:00 [medline]
PHST- 2021/01/30 00:00 [pmc-release]
AID - genes12020201 [pii]
AID - genes-12-00201 [pii]
AID - 10.3390/genes12020201 [doi]
PST - epublish
SO  - Genes (Basel). 2021 Jan 30;12(2):201. doi: 10.3390/genes12020201.