Repair of DNA double-strand breaks in RNAPI- and RNAPII-transcribed loci

Area of Science:

• Molecular Biology
• Genetics
• Cellular Biology

Background:

• DNA double-strand breaks (DSBs) are critical DNA lesions.
• Endogenous DSBs often arise in transcriptionally active genomic regions.
• Specific pathways may handle DSBs in transcribed loci.

Purpose of the Study:

• To provide an updated overview of transcription-coupled DSB repair (TC-DSBR) pathways.
• To highlight commonalities and differences in TC-DSBR for RNA Polymerase I (RNAPI) and RNA Polymerase II (RNAPII) transcribed loci.
• To identify outstanding questions in the field of TC-DSBR.

Main Methods:

• Graphical Review synthesizing current literature.
• Focus on DSBs in RNAPI and RNAPIl transcribed regions.
• Analysis of molecular mechanisms including transcriptional repression, chromatin signaling, RNA involvement, and DSB mobility.

Main Results:

• DSBs in transcribed loci are managed by distinct TC-DSBR pathways.
• These pathways share common features but also exhibit locus-specific differences.
• Key components include transcriptional repression, chromatin modifications, RNA participation, and DSB relocation.

Conclusions:

• TC-DSBR pathways are crucial for maintaining genome integrity at active genes.
• Understanding these pathways offers insights into DNA repair dynamics.
• Further research is needed to fully elucidate the complexities of TC-DSBR.