The E2F1 transcription factor and RB tumor suppressor moonlight as DNA repair factors

Cell Cycle. 2020 Sep;19(18):2260-2269. doi: 10.1080/15384101.2020.1801190. Epub 2020 Aug 13.

Abstract

The E2F1 transcription factor and RB tumor suppressor are best known for their roles in regulating the expression of genes important for cell cycle progression but, they also have transcription-independent functions that facilitate DNA repair at sites of damage. Depending on the type of DNA damage, E2F1 can recruit either the GCN5 or p300/CBP histone acetyltransferases to deposit different histone acetylation marks in flanking chromatin. At DNA double-strand breaks, E2F1 also recruits RB and the BRG1 ATPase to remodel chromatin and promote loading of the MRE11-RAD50-NBS1 complex. Knock-in mouse models demonstrate important roles for E2F1 post-translational modifications in regulating DNA repair and physiological responses to DNA damage. This review highlights how E2F1 moonlights in DNA repair, thus revealing E2F1 as a versatile protein that recruits many of the same chromatin-modifying enzymes to sites of DNA damage to promote repair that it recruits to gene promoters to regulate transcription.

Keywords: ATM/ATR; BRG1; E2F1; GCN5; TopBP1; p300/CBP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Acetylation
  • Animals
  • Chromatin Assembly and Disassembly
  • DNA Damage*
  • DNA Repair*
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism*
  • Histones / metabolism
  • Humans
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism*
  • p300-CBP Transcription Factors / metabolism

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Histones
  • Retinoblastoma Protein
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor