The dynamic interplay in chromatin remodeling factors polycomb and trithorax proteins in response to DNA damage

Shuang Liu1, Yongguang Tao, Xiang Chen

  • 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Molecular Biology Reports
|December 29, 2011
PubMed

Insights

Polycomb (PcG) and Trithorax (TrxG) proteins dynamically interact at DNA double-strand break sites, influencing DNA repair pathways. Understanding this interplay is crucial for cancer mechanisms and developing anti-DNA damage response drugs.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Research

Background:

  • Polycomb group (PcG) and Trithorax group (TrxG) proteins are key epigenetic regulators.
  • Their dynamic interplay is implicated in cellular responses to DNA damage.
  • Chromatin remodeling is essential for DNA damage response (DDR) and repair.

Purpose of the Study:

  • To investigate the role of PcG and TrxG protein interplay in DNA double-strand break (DSB) repair.
  • To elucidate the involvement of PcG and TrxG proteins in homologous recombination (HR) and nonhomologous end joining (NHEJ) pathways.
  • To explore the implications of PcG/TrxG dynamics in DDR for carcinogenesis and therapeutic strategies.

Main Methods:

  • Analysis of PcG and TrxG protein localization at DSB sites.
  • Investigating the impact of PcG and TrxG on chromatin remodeling during DDR.
  • Studying the interaction of tumor suppressor genes with TrxGs in DDR and repair pathways.

Main Results:

  • PcG and TrxG proteins are recruited to DSB sites, suggesting direct involvement in repair.
  • PcG proteins exhibit resistance to chromatin relaxation during DDR.
  • Tumor suppressor genes interact with TrxGs, participating in DDR and repair.

Conclusions:

  • The dynamic interplay between PcG and TrxG proteins is critical for effective DNA damage response and repair.
  • Dysregulation of PcG/TrxG interplay may contribute to carcinogenesis.
  • Targeting the DDR pathway involving PcG and TrxG proteins offers potential for novel anti-cancer drug development.

Related Concept Videos

Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...