Recognition of RNA Polymerase II and Transcription Bubbles by XPG,CSB and TFIIH: Insights for Transcription-Coupled Repair and CockayneSyndrome

Journal Article · Fri Oct 21 04:00:00 EDT 2005 · Molecular Cell

DOI:https://doi.org/10.1016/j.molcel.2005.09.022· OSTI ID:881848

Sarker, Altaf H; Tsutakawa, Susan E; Kostek, Seth; Ng, Cliff; Shin, David S; Peris, Marian; Campeau, Eric; Tainer, John A; Nogales, Eva; Cooper, Priscilla K

Loss of a non-enzymatic function of XPG results in defective transcription-coupled repair (TCR), Cockayne syndrome (CS) and early death, but the molecular basis for these phenotypes is unknown. Mutation of CSB, CSA, or the TFIIH helicases XPB and XPD can also cause defective TCR and CS. We show that XPG interacts with elongating RNA polymerase II(RNAPII) in the cell and binds stalled RNAPII ternary complexes in vitro both independently and cooperatively with CSB. XPG binds transcription-sized DNA bubbles through two domains not required for incision and functionally interacts with CSB on these bubbles to stimulate its ATPase activity. Bound RNAPII blocks bubble incision by XPG, but an ATP hydrolysis-dependent process involving TFIIH creates access to the junction, allowing incision. Together, these results implicate coordinated recognition of stalled transcription by XPG and CSB in TCR initiation and suggest that TFIIH-dependent remodeling of stalled RNAPII without release may be sufficient to allow repair.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director, Office of Science. Office of Biological andEnvironmental Research. Life Sciences Division; National Institutes ofHealth
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 881848
• Report Number(s): LBNL--58942
• Journal Information: Molecular Cell, Journal Name: Molecular Cell Vol. 20
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BUBBLES
DNA
IN VITRO
MUTATIONS
REPAIR
RNA POLYMERASES
TRANSCRIPTION