PMID- 30276254
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2374-7943 (Print)
IS  - 2374-7951 (Electronic)
IS  - 2374-7943 (Linking)
VI  - 4
IP  - 9
DP  - 2018 Sep 26
TI  - A Lamin-Binding Ligand Inhibits Homologous Recombination Repair of DNA 
      Double-Strand Breaks.
PG  - 1201-1210
LID - 10.1021/acscentsci.8b00379 [doi]
AB  - Nuclear lamins are type V intermediate filament proteins. Lamins, including LA, 
      LB1, LB2, and LC, are the major protein components forming the nuclear lamina to 
      support the mechanical stability of the mammalian cell nucleus. Increasing 
      evidence has shown that LA participates in homologous recombination (HR) repair 
      of DNA double-strand breaks (DSBs) . However, the mechanisms underlying this 
      process are incompletely understood. We recently identified the first 
      lamin-binding ligand 1 (LBL1) that directly binds LA and inhibited cancer cell 
      growth. We provided here further mechanistic investigations of LBL1 and revealed 
      that LA interacts with the HR recombinase Rad51 to protect Rad51 from 
      degradation. LBL1 inhibits LA-Rad51 interaction leading to accelerated 
      proteasome-mediated degradation of Rad51, culminating in inhibition of HR repair 
      of DSBs. These results uncover a novel post-translational regulation of Rad51 by 
      LA and suggest that targeting the LA-Rad51 axis may represent a promising 
      strategy to develop cancer therapeutics.
FAU - Li, Bingbing X
AU  - Li BX
AD  - Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon 
      Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 
      97239, United States.
FAU - Chen, Jingjin
AU  - Chen J
AD  - Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon 
      Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 
      97239, United States.
FAU - Chao, Bo
AU  - Chao B
AD  - Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon 
      Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 
      97239, United States.
FAU - Zheng, Yixian
AU  - Zheng Y
AD  - Department of Embryology, Carnegie Institution for Science, 3520 San Martin 
      Drive, Baltimore, Maryland 21218, United States.
FAU - Xiao, Xiangshu
AU  - Xiao X
AD  - Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon 
      Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 
      97239, United States.
AD  - Knight Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson 
      Park Road, Portland, Oregon 97239, United States.
LA  - eng
GR  - R01 CA211866/CA/NCI NIH HHS/United States
GR  - R01 GM122820/GM/NIGMS NIH HHS/United States
GR  - R21 CA220061/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20180917
PL  - United States
TA  - ACS Cent Sci
JT  - ACS central science
JID - 101660035
PMC - PMC6161055
COIS- The authors declare no competing financial interest.
EDAT- 2018/10/03 06:00
MHDA- 2018/10/03 06:01
PMCR- 2018/09/17
CRDT- 2018/10/03 06:00
PHST- 2018/06/18 00:00 [received]
PHST- 2018/10/03 06:00 [entrez]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2018/10/03 06:01 [medline]
PHST- 2018/09/17 00:00 [pmc-release]
AID - 10.1021/acscentsci.8b00379 [doi]
PST - ppublish
SO  - ACS Cent Sci. 2018 Sep 26;4(9):1201-1210. doi: 10.1021/acscentsci.8b00379. Epub 
      2018 Sep 17.