ausblenden:
Schlagwörter:
-
Zusammenfassung:
UV-induced cyclobutane pyrimidine dimers (CPDs)
in the template DNA strand stall transcription elongation
by RNA polymerase II (Pol II). If the nucleotide
excision repair machinery does not promptly remove
the CPDs, stalled Pol II creates a roadblock for DNA
replication and subsequent rounds of transcription.
Here we present evidence that Pol II has an intrinsic
capacity for translesion synthesis (TLS) that enables
bypass of the CPD with or without repair. Translesion
synthesis depends on the trigger loop and bridge
helix, the two flexible regions of the Pol II subunit
Rpb1 that participate in substrate binding, catalysis,
and translocation. Substitutions in Rpb1 that
promote lesion bypass in vitro increase UV resistance
in vivo, and substitutions that inhibit lesion
bypass decrease cell survival after UV irradiation.
Thus, translesion transcription becomes essential
for cell survival upon accumulation of the unrepaired
CPD lesions in genomic DNA.
