PMID- 37590191
OWN - NLM
STAT- MEDLINE
DCOM- 20230821
LR  - 20230823
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 8
DP  - 2023
TI  - The CST complex facilitates cell survival under oxidative genotoxic stress.
PG  - e0289304
LID - 10.1371/journal.pone.0289304 [doi]
LID - e0289304
AB  - Genomic DNA is constantly exposed to a variety of genotoxic stresses, and it is 
      crucial for organisms to be equipped with mechanisms for repairing the damaged 
      genome. Previously, it was demonstrated that the mammalian CST (CTC1-STN1-TEN1) 
      complex, which was originally identified as a single-stranded DNA-binding 
      trimeric protein complex essential for telomere maintenance, is required for 
      survival in response to hydroxyurea (HU), which induces DNA replication fork 
      stalling. It is still unclear, however, how the CST complex is involved in the 
      repair of diverse types of DNA damage induced by oxidizing agents such as H2O2. 
      STN1 knockdown (KD) sensitized HeLa cells to high doses of H2O2. While H2O2 
      induced DNA strand breaks throughout the cell cycle, STN1 KD cells were as 
      resistant as control cells to H2O2 treatment when challenged in the G1 phase of 
      the cell cycle, but they were sensitive when exposed to H2O2 in S/G2/M phase. 
      STN1 KD cells showed a failure of DNA synthesis and RAD51 foci formation upon 
      H2O2 treatment. Chemical inhibition of RAD51 in shSTN1 cells did not exacerbate 
      the sensitivity to H2O2, implying that the CST complex and RAD51 act in the same 
      pathway. Collectively, our results suggest that the CST complex is required for 
      maintaining genomic stability in response to oxidative DNA damage, possibly 
      through RAD51-dependent DNA repair/protection mechanisms.
CI  - Copyright: (c) 2023 Hara et al. This is an open access article distributed under 
      the terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Hara, Tomohiko
AU  - Hara T
AUID- ORCID: 0009-0000-9443-3891
AD  - Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, 
      Kyoto, Japan.
AD  - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, 
      Japan.
FAU - Nakaoka, Hidenori
AU  - Nakaoka H
AUID- ORCID: 0000-0001-8465-5853
AD  - Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, 
      Kyoto, Japan.
AD  - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, 
      Japan.
FAU - Miyoshi, Tomoicihiro
AU  - Miyoshi T
AD  - Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, 
      Kyoto, Japan.
AD  - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, 
      Japan.
AD  - Laboratory for Retrotransposon Dynamics, RIKEN Center for Integrative Medical 
      Sciences, Yokohama, Japan.
FAU - Ishikawa, Fuyuki
AU  - Ishikawa F
AUID- ORCID: 0000-0002-5580-2305
AD  - Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, 
      Kyoto, Japan.
AD  - Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, 
      Japan.
LA  - eng
SI  - Dryad/10.5061/dryad.12jm63z3r
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230817
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Shelterin Complex)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Humans
MH  - Animals
MH  - *Shelterin Complex
MH  - Cell Survival
MH  - HeLa Cells
MH  - *Hydrogen Peroxide/pharmacology
MH  - Telomere
MH  - DNA Damage
MH  - Mammals
PMC - PMC10434909
COIS- The authors have declared that no competing interests exist.
EDAT- 2023/08/17 18:42
MHDA- 2023/08/21 06:42
PMCR- 2023/08/17
CRDT- 2023/08/17 13:33
PHST- 2023/03/22 00:00 [received]
PHST- 2023/07/15 00:00 [accepted]
PHST- 2023/08/21 06:42 [medline]
PHST- 2023/08/17 18:42 [pubmed]
PHST- 2023/08/17 13:33 [entrez]
PHST- 2023/08/17 00:00 [pmc-release]
AID - PONE-D-23-08516 [pii]
AID - 10.1371/journal.pone.0289304 [doi]
PST - epublish
SO  - PLoS One. 2023 Aug 17;18(8):e0289304. doi: 10.1371/journal.pone.0289304. 
      eCollection 2023.