K6-linked SUMOylation of BAF regulates nuclear integrity and DNA replication in mammalian cells

Proc Natl Acad Sci U S A. 2020 May 12;117(19):10378-10387. doi: 10.1073/pnas.1912984117. Epub 2020 Apr 24.

Abstract

Barrier-to-autointegration factor (BAF) is a highly conserved protein in metazoans that has multiple functions during the cell cycle. We found that BAF is SUMOylated at K6, and that this modification is essential for its nuclear localization and function, including nuclear integrity maintenance and DNA replication. K6-linked SUMOylation of BAF promotes binding and interaction with lamin A/C to regulate nuclear integrity. K6-linked SUMOylation of BAF also supports BAF binding to DNA and proliferating cell nuclear antigen and regulates DNA replication. SENP1 and SENP2 catalyze the de-SUMOylation of BAF at K6. Disrupting the SUMOylation and de-SUMOylation cycle of BAF at K6 not only disturbs nuclear integrity, but also induces DNA replication failure. Taken together, our findings demonstrate that SUMOylation at K6 is an important regulatory mechanism that governs the nuclear functions of BAF in mammalian cells.

Keywords: SUMOylation; barrier-to-autointegration factor (BAF); cell cycle; lamin A/C; nuclear integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • DNA / metabolism
  • DNA Replication / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Lamin Type A / metabolism
  • Lysine / metabolism
  • Membrane Proteins / metabolism
  • Nuclear Localization Signals / genetics
  • Nuclear Proteins / metabolism
  • Protein Binding / physiology
  • Sumoylation / physiology

Substances

  • BANF1 protein, human
  • DNA-Binding Proteins
  • LMNA protein, human
  • Lamin Type A
  • Membrane Proteins
  • Nuclear Localization Signals
  • Nuclear Proteins
  • DNA
  • Lysine