Chemistry Reference
In-Depth Information
Figure 6.1
Base excision repair mechanism in mammalian cells
have raised some doubts about the role of XPE in excision repair.
14 - 16
The recogni-
tion assembly recruits the TFIIH transcription/repair factor, which contains six
polypeptides including helicases XPB and XPD that unwind the DNA around the
damage site; the XPG and XPF-ERCC1 subunits are responsible for the 3
′
and 5
′
dual incisions, respectively. The dual-incision leads to the removal of a single-
stranded fragment of DNA with a single-strand gap of 25
30 nucleotides. The result-
ing gap in DNA is fi lled by DNA polymerase d or e (Table 6.2) by copying the
undamaged strand. Proliferating cell nuclear antigen (PCNA) assists the DNA
polymerase in the reaction, and replication protein A (RPA) protects the other
DNA strand from degradation during NER. Finally, DNA ligase I seals the nicks to
fi nish NER.
17,18
∼
Mismatch Repair
MMR provides several genetic stabilization functions; it corrects errors of DNA
replication, ensures the fi delity of genetic recombination and participates in the
earliest steps of checkpoint and apoptotic responses to several classes of DNA
damage. Hence, a primary function of the MMR pathway is to correct persistent
DNA replication errors and avoid the accumulation of deleterious mutations. MMR
