Asymmetric condensin loop extrusion is regulated by RPA-coated single-stranded DNA in quiescent cells

Area of Science:

• Molecular Biology
• Genetics
• Chromatin Biology

Background:

• Structural Maintenance of Chromosomes (SMC) complexes organize the genome through loop extrusion, impacting DNA-dependent processes.
• The precise mechanisms linking transcription to SMC complex function and loop extrusion directionality in cells remain unclear.

Purpose of the Study:

• To investigate the relationship between condensin loop extrusion and transcription in a quiescent yeast model.
• To elucidate the temporal mechanisms of condensin targeting to gene promoters.

Main Methods:

• Utilized a quiescent yeast model for temporal dissection of condensin targeting.
• Employed targeted degradation experiments to study condensin recruitment and function.
• Analyzed a condensin mutant to determine loop extrusion directionality in vivo.

Main Results:

• Condensin gradually relocates to transcribed gene promoters during quiescence entry.
• Transcription-generated topological stress leads to RPA-bound single-stranded DNA at promoters, serving as condensin loading sites and extrusion barriers.
• Condensin was observed to extrude loops asymmetrically within cells.

Conclusions:

• RPA antagonism is proposed as a universal regulator of SMC complex function.
• Transcription-induced topological stress and RPA binding are critical for regulating condensin activity and genome organization.