RB·E2F1 complex mediates DNA damage responses through transcriptional regulation of ZBRK1

Ching Chun Liao, Connie Y. Tsai, Wen Chang Chang, Wen Hwa Lee, Ju Ming Wang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

RB plays an essential role in DNA damage-induced growth arrest and regulates the expression of several factors essential for DNA repair machinery. However, how RB coordinates DNA damage response through transcriptional regulation of genes involved in growth arrest remains largely unexplored. We examined whether RB can mediate the response to DNA damage through modulation of ZBRK1, a zinc finger-containing transcriptional repressor that can modulate the expression of GADD45A, a DNA damage response gene, to induce cell cycle arrest in response to DNA damage. We found that the ZBRK1 promoter contains an authentic E2F-recognition sequence that specifically binds E2F1, but not E2F4 or E2F6, together with chromatin remodeling proteins CtIP and CtBP to form a repression complex that suppresses ZBRK1 transcription. Furthermore, loss of RB-mediated transcriptional repression led to an increase in ZBRK1 transcript levels, correlating with increased sensitivity to ultraviolet (UV) and methyl methanesulfonate-induced DNA damage. Taken together, these results suggest that the RB·CtIP (CtBP interacting protein)/CtBP (C terminus-binding protein) /E2F1 complex plays a critical role in ZBRK1 transcriptional repression, and loss of this repression may contribute to cellular sensitivity of DNA damage, ultimately leading to carcinogenesis.

Original languageEnglish
Pages (from-to)33134-33143
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number43
DOIs
Publication statusPublished - Oct 22 2010
Externally publishedYes

Fingerprint

DNA Damage
DNA
Methyl Methanesulfonate
Genes
Chromatin Assembly and Disassembly
Zinc Fingers
Growth
Cell Cycle Checkpoints
Protein C
DNA Repair
Transcription
Carrier Proteins
Carcinogenesis
Chromatin
Machinery
Zinc
Proteins
Repair
Cells
Modulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

RB·E2F1 complex mediates DNA damage responses through transcriptional regulation of ZBRK1. / Liao, Ching Chun; Tsai, Connie Y.; Chang, Wen Chang; Lee, Wen Hwa; Wang, Ju Ming.

In: Journal of Biological Chemistry, Vol. 285, No. 43, 22.10.2010, p. 33134-33143.

Research output: Contribution to journalArticle

Liao, Ching Chun ; Tsai, Connie Y. ; Chang, Wen Chang ; Lee, Wen Hwa ; Wang, Ju Ming. / RB·E2F1 complex mediates DNA damage responses through transcriptional regulation of ZBRK1. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 43. pp. 33134-33143.
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