Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• DNA damage poses a significant threat to cellular processes, including transcription.
• Transcription-blocking lesions impede RNA polymerase II, leading to replication-transcription conflicts and genome instability.
• Cellular mechanisms to counteract DNA damage during transcription are complex and not fully understood.

Purpose of the Study:

• To identify factors involved in the transcription stress response following DNA damage.
• To elucidate the role of the elongation factor ELOF1 in DNA damage repair and genome stability.

Main Methods:

• Genome-wide CRISPR-Cas9 screening to identify key factors in transcription stress response.
• Investigating the function of ELOF1 in transcription-coupled nucleotide excision repair (TC-NER).
• Assessing ELOF1's role in modulating transcription and preventing replication stress.

Main Results:

• The elongation factor ELOF1 was identified as crucial for the transcription stress response.
• ELOF1 plays a conserved role in TC-NER, promoting the recruitment of UVSSA and TFIIH to repair DNA lesions.
• ELOF1 protects against transcription-mediated replication stress, thereby preserving genome stability.

Conclusions:

• ELOF1 is a key player in the cellular response to DNA damage affecting transcription.
• ELOF1 facilitates the repair of transcription-blocking lesions via TC-NER and safeguards genome integrity by mitigating replication stress.
• ELOF1 employs dual mechanisms to protect the transcription machinery from DNA damage.