Characterization of LGALS3 (galectin-3) as a player in DNA damage response

Cancer Biol Ther. 2014 Jul;15(7):840-50. doi: 10.4161/cbt.28873. Epub 2014 Apr 22.

Abstract

DNA damage repair (DDR) is an orchestrated process encompassing the injury detection to its complete resolution. DNA double-strand break lesions are repaired mainly by two distinct mechanisms: the error-free homologous recombination (HR) and the error-prone non-homologous end-joining. Galectin-3 (GAL3) is the unique member of the chimeric galectins subfamily and is reported to be involved in several cancer development and progression related events. Recently our group described a putative protein interaction between GAL3 and BARD1, the main partner of breast and ovarian cancer susceptibility gene product BRCA1, both involved in HR pathway. In this report we characterized GAL3/BARD1 protein interaction and evaluated the role of GAL3 in DDR pathways using GAL3 silenced human cells exposed to different DNA damage agents. In the absence of GAL3 we observed a delayed DDR response activation, as well as a decrease in the G 2/M cell cycle checkpoint arrest associated with HR pathway. Moreover, using a TAP-MS approach we also determined the protein interaction network of GAL3.

Keywords: BARD1; BRCA1; DNA damage; cancer; galectin-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • BRCA1 Protein / metabolism
  • Carboplatin / pharmacology
  • DNA Damage*
  • DNA Repair*
  • Etoposide / pharmacology
  • G2 Phase Cell Cycle Checkpoints
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Gene Silencing
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mitomycin / pharmacology
  • Protein Interaction Maps
  • Signal Transduction
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • Galectin 3
  • LGALS3 protein, human
  • Tumor Suppressor Proteins
  • Mitomycin
  • Etoposide
  • Carboplatin
  • BARD1 protein, human
  • Ubiquitin-Protein Ligases