Transcriptional regulation and chromatin dynamics at DNA double-strand breaks

Sunwoo Min1,2, Jae-Hoon Ji3, Yungyeong Heo4,5

  • 1Department of Biochemistry, Ajou University School of Medicine, Suwon, 16499, Korea. smin1221@gmail.com.

Insights

The ISWI family of chromatin remodelers coordinates DNA damage response and gene silencing in active transcription sites. This highlights their role in modulating the epigenetic environment for DNA repair.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Epigenetics

Background:

  • DNA double-strand breaks disrupt chromatin integrity and trigger DNA damage responses.
  • Active transcription near DNA lesions can be transiently suppressed by interactions between DNA damage response factors and polycomb repressive complexes.
  • Epigenetic modifications influence DNA damage response signaling and transcriptional repression.

Purpose of the Study:

  • To discuss the role of the ISWI family of chromatin remodeling factors in coordinating DNA damage response and transcriptional repression.
  • To highlight the direct modulation of the epigenetic environment by ISWI factors, particularly in transcriptionally active regions.

Main Methods:

  • The study is a discussion/review of existing research.
  • Focuses on the interplay between chromatin remodeling, DNA damage response, and transcriptional regulation.

Main Results:

  • ISWI chromatin remodelers coordinate DNA damage response and transcriptional repression in active regions.
  • Epigenetic modulation is crucial for efficient DNA damage response signaling and gene silencing.
  • Active chromatin context and RNA transcripts from G1 phase promote homologous recombination repair.

Conclusions:

  • The ISWI family of chromatin remodelers plays a key role in managing the cellular response to DNA damage in transcriptionally active chromatin.
  • Understanding these mechanisms is vital for comprehending genome stability and repair processes.

Related Concept Videos

Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.8K
Duplication of Chromatin Structure02:05

Duplication of Chromatin Structure

The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
5.6K
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...
50.9K
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
7.1K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.9K
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...
9.4K