The Paf1 complex is required for RNA polymerase II removal in response to DNA damage

Area of Science:

• Molecular Biology
• Cellular Biology
• Biochemistry

Background:

• RNA polymerase II (RNAPII) degradation is a critical DNA damage response.
• The precise mechanism controlling RNAPII subunit Rpb1 degradation remains unclear.

Purpose of the Study:

• To elucidate the mechanism by which Rpb1 is polyubiquitinated and degraded following DNA damage.
• To investigate the role of the polymerase-associated factor 1 (PAF1C) complex in this process.

Main Methods:

• Investigated protein-protein interactions and complex assembly.
• Utilized techniques to study ubiquitination and proteasomal degradation.
• Examined the recruitment of protein complexes to DNA lesions.

Main Results:

• Identified a multistep pathway involving PAF1C in regulating RNAPII levels post-DNA damage.
• Demonstrated that PAF1C stimulates Elongin-Cullin E3 ligase-mediated Rpb1 polyubiquitination and degradation.
• Showed that Spt5 dephosphorylation and Rad26 recruitment are key initiating steps for Rpb1 removal.

Conclusions:

• The intact PAF1C complex plays a crucial role in regulating the RNAPII pool during the DNA damage response.
• This pathway involves the coordinated action of PAF1C, Rad26, and the Elongin-Cullin complex to remove damaged RNAPII.
• Uncovered a novel mechanism for controlling RNAPII stability in response to genotoxic stress.