KAP1 facilitates reinstatement of heterochromatin after DNA replication

Nucleic Acids Res. 2018 Sep 28;46(17):8788-8802. doi: 10.1093/nar/gky580.

Abstract

During cell division, maintenance of chromatin features from the parental genome requires their proper establishment on its newly synthetized copy. The loss of epigenetic marks within heterochromatin, typically enriched in repetitive elements, endangers genome stability and permits chromosomal rearrangements via recombination. However, how histone modifications associated with heterochromatin are maintained across mitosis remains poorly understood. KAP1 is known to act as a scaffold for a repressor complex that mediates local heterochromatin formation, and was previously demonstrated to play an important role during DNA repair. Accordingly, we investigated a putative role for this protein in the replication of heterochromatic regions. We first found that KAP1 associates with several DNA replication factors including PCNA, MCM3 and MCM6. We then observed that these interactions are promoted by KAP1 phosphorylation on serine 473 during S phase. Finally, we could demonstrate that KAP1 forms a complex with PCNA and the histone-lysine methyltransferase Suv39h1 to reinstate heterochromatin after DNA replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromatin Assembly and Disassembly / genetics*
  • DNA Replication / physiology*
  • HEK293 Cells
  • HeLa Cells
  • Heterochromatin / metabolism*
  • Humans
  • K562 Cells
  • Methyltransferases / metabolism
  • Mice
  • NIH 3T3 Cells
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Processing, Post-Translational
  • Repressor Proteins / metabolism
  • Tripartite Motif-Containing Protein 28 / physiology*

Substances

  • Heterochromatin
  • Proliferating Cell Nuclear Antigen
  • Repressor Proteins
  • SUV39H1 protein, human
  • Suv39h1 protein, mouse
  • Methyltransferases
  • TRIM28 protein, human
  • Trim28 protein, mouse
  • Tripartite Motif-Containing Protein 28