TY - JOUR
T1 - STK19 facilitates the clearance of lesion-stalled RNAPII during transcription-coupled DNA repair
AU - van den Heuvel, Diana
AU - Rodríguez-Martínez, Marta
AU - van der Meer, Paula J
AU - Moreno, Nicolas Nieto
AU - Park, Jiyoung
AU - Kim, Hyun-Suk
AU - van Schie, Janne J M
AU - Wondergem, Annelotte P
AU - D'Souza, Areetha
AU - Yakoub, George
AU - Herlihy, Anna E
AU - Kashyap, Krushanka
AU - Boissière, Thierry
AU - Walker, Jane
AU - Mitter, Richard
AU - Apelt, Katja
AU - de Lint, Klaas
AU - Kirdök, Idil
AU - Ljungman, Mats
AU - Wolthuis, Rob M F
AU - Cramer, Patrick
AU - Schärer, Orlando D
AU - Kokic, Goran
AU - Svejstrup, Jesper Q
AU - Luijsterburg, Martijn S
PY - 2024/7/22
Y1 - 2024/7/22
N2 - Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and TFIIH around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a new TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryo-EM and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.
AB - Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and TFIIH around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a new TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryo-EM and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.
U2 - 10.1101/2024.07.22.604575
DO - 10.1101/2024.07.22.604575
M3 - Article
C2 - 39091731
SN - 2692-8205
JO - bioRxiv : the preprint server for biology
JF - bioRxiv : the preprint server for biology
ER -