**4.5 Mismatch repair (MMR)**

The MMR system is responsible for the post-replicative repair of mismatches and small single stranded DNA loops, and is essential to the prevention of recombination between homologous DNA sequences. Although MMR repair in eukaryotic cells is not fully understood, studies of this mechanism in bacteria have contributed considerably to our understanding of this pathway. MMR is dependent on three highly conserved proteins: MutS, MutL, and MutH. In eukaryotes, homologous proteins as PCNA, RPA, HMGB1, RFC, and ligase I participate and coordinate the MMR process. Eukaryotic cells that are deficient in MMR have a 10-1,000-fold increase in mutation rates (Kunkel & Erie, 2005). In another study, MMR deficient mice showed an increase in PAH-induced lymphoma compared to controls (Zienolddiny, et al., 2006). MMR corrects strand-specific base mispairs and small loop structures. Furthermore, this mechanism recognizes smaller base analoges as mispairs that are participating in oxidative DNA damage repair. Cells deficient in the hMLH1 protein (essential for MMR initiation) have a reduced repair activity when exposed to anthracene (Desler, et al., 2009). This result indicates that MMR has a probable role in DNA repair response resulting from PAH exposure.

### **4.6 Other repair mechanisms**

Further studies are necessary to confirm two other possible mechanisms involved in DNA repair following PAH exposure: non-homologous end joining (NHEJ) and transcription coupled repair (TCR). NHEJ appears to participate in DNA repair after PAH exposure. A recent report described that the V3-3 CHO cell line (NHEJ-deficient), showed a statistically significant dose-dependent enhancement during induced sister chromatid exchanges under PAH exposure. This result indicates that this process is important in DNA repair (Meschini, et al., 2010).

Some adducts perform alterations to the transcription process. The current model for TCR is dependent on the stalling of RNA pol II. Some PAHs such as BPDE and B[c]PhDE produce adducts repaired by TCR, while other studies indicate that PAHs such as B[g]Ch-DE and DB[a,l]P-DE also produce adducts. The efficiency and rate for repairing DNA depends of intrinsic adduct properties (Zhong, et al., 2010). For a complete review of this process we suggest consulting Scicchitano (2005).
