Bypass of DNA interstrand crosslinks by a Rev1–DNA polymerase ζ complex
| Autor: | Rachel Bezalel-Buch, Young K. Cheun, Orlando D. Schärer, Upasana Roy, Peter M. J. Burgers |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
DNA Replication
Saccharomyces cerevisiae Proteins DNA Repair DNA polymerase AcademicSubjects/SCI00010 viruses Interstrand crosslink DNA-Directed DNA Polymerase Saccharomyces cerevisiae Genome Integrity Repair and Replication 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine ICL repair Genetics 030304 developmental biology 0303 health sciences biology Chemistry Oligonucleotide DNA Nucleotidyltransferases Chromosome Structures 030220 oncology & carcinogenesis Multiprotein Complexes Nitrogen Mustard Compounds Biophysics biology.protein REV1 Elongation Linker DNA Damage |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | DNA polymerase ζ (Pol ζ) and Rev1 are essential for the repair of DNA interstrand crosslink (ICL) damage. We have used yeast DNA polymerases η, ζ and Rev1 to study translesion synthesis (TLS) past a nitrogen mustard-based interstrand crosslink (ICL) with an 8-atom linker between the crosslinked bases. The Rev1–Pol ζ complex was most efficient in complete bypass synthesis, by 2–3 fold, compared to Pol ζ alone or Pol η. Rev1 protein, but not its catalytic activity, was required for efficient TLS. A dCMP residue was faithfully inserted across the ICL-G by Pol η, Pol ζ, and Rev1–Pol ζ. Rev1–Pol ζ, and particularly Pol ζ alone showed a tendency to stall before the ICL, whereas Pol η stalled just after insertion across the ICL. The stalling of Pol η directly past the ICL is attributed to its autoinhibitory activity, caused by elongation of the short ICL-unhooked oligonucleotide (a six-mer in our study) by Pol η providing a barrier to further elongation of the correct primer. No stalling by Rev1–Pol ζ directly past the ICL was observed, suggesting that the proposed function of Pol ζ as an extender DNA polymerase is also required for ICL repair. |
| Databáze: | OpenAIRE |
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