PMID- 33671338
OWN - NLM
STAT- MEDLINE
DCOM- 20210413
LR  - 20221206
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 17
TI  - The Multiple Cellular Roles of SMUG1 in Genome Maintenance and Cancer.
LID - 10.3390/ijms22041981 [doi]
LID - 1981
AB  - Single-strand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to 
      remove uracil and certain oxidized bases from DNA during base excision repair 
      (BER). This review provides a historical characterization of SMUG1 and 
      5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. 
      Biochemical and structural analyses provide remarkable insight into the mechanism 
      of this glycosylase: SMUG1 has a unique helical wedge that influences damage 
      recognition during repair. Rodent studies suggest that, while SMUG1 shares 
      substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can 
      have unique cellular phenotypes. This review highlights the multiple roles SMUG1 
      may play in preserving genome stability, and how the loss of SMUG1 activity may 
      promote cancer. Finally, we discuss recent studies indicating SMUG1 has 
      moonlighting functions beyond BER, playing a critical role in RNA processing 
      including the RNA component of telomerase.
FAU - Raja, Sripriya
AU  - Raja S
AUID- ORCID: 0000-0001-6853-869X
AD  - Molecular Pharmacology Graduate Program, School of Medicine, University of 
      Pittsburgh, Pittsburgh, PA 15213, USA.
AD  - UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
FAU - Van Houten, Bennett
AU  - Van Houten B
AUID- ORCID: 0000-0002-4009-2478
AD  - Molecular Pharmacology Graduate Program, School of Medicine, University of 
      Pittsburgh, Pittsburgh, PA 15213, USA.
AD  - UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213, USA.
AD  - Department of Pharmacology and Chemical Biology, School of Medicine, University 
      of Pittsburgh, Pittsburgh, PA 15213, USA.
LA  - eng
GR  - R35 ES031638/ES/NIEHS NIH HHS/United States
GR  - R01ES019566, R35ES031638/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20210217
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Nucleosomes)
RN  - EC 3.2.2.- (Uracil-DNA Glycosidase)
SB  - IM
MH  - Animals
MH  - Cytoprotection
MH  - *Genome
MH  - Humans
MH  - Neoplasms/*enzymology/*genetics
MH  - Nucleosomes/metabolism
MH  - Substrate Specificity
MH  - Uracil-DNA Glycosidase/*metabolism
PMC - PMC7922111
OTO - NOTNLM
OT  - 5-hmdU
OT  - DNA damage
OT  - SMUG1
OT  - base excision repair
OT  - cancer
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/07 06:00
MHDA- 2021/04/14 06:00
PMCR- 2021/02/17
CRDT- 2021/03/06 01:10
PHST- 2021/01/23 00:00 [received]
PHST- 2021/02/12 00:00 [revised]
PHST- 2021/02/13 00:00 [accepted]
PHST- 2021/03/06 01:10 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/04/14 06:00 [medline]
PHST- 2021/02/17 00:00 [pmc-release]
AID - ijms22041981 [pii]
AID - ijms-22-01981 [pii]
AID - 10.3390/ijms22041981 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 17;22(4):1981. doi: 10.3390/ijms22041981.