Localisation of human Y - family DNA polymerase κ : relationship to PCNA foci

All cells have evolved a variety of pathways for repairing different types of DNA damage. Despite the efficiency of these pathways, unrepaired lesions remain in the DNA during DNA replication, and most types of DNA damage block the progress of the replication machinery. The replicative DNA polymerases are very efficient and processive, and replicate DNA with high fidelity. However, they are unable to accommodate damaged DNA bases in their active sites and such lesions block their progress. A major way in which mammalian cells overcome this barrier is to use specialised translesion synthesis (TLS) polymerases. These polymerases have low efficiencies and fidelities, but are able to replicate DNA past different types of damage (reviewed by Lehmann, 2002; Prakash and Prakash, 2002). Four of these TLS polymerases belong to the recently discovered Y-family (Ohmori et al., 2001). DNA polymerase η (polη) is able to replicate DNA containing the major UV photoproduct, the cyclobutane pyrimidine dimer (CPD) with similar efficiency to undamaged DNA, and in the case of the T-T CPD, the 'correct' nucleotides (A-A) are usually inserted opposite the damage (Johnson et al., 2000b; Masutani et al., 2000). Deficiency in polη results in the variant form of xeroderma pigmentosum (Broughton et al., 2002; Johnson et al., 1999; Masutani et al., 1999). Polι is a paralog of polη (Tissier et al., 2000), but despite extensive studies on its activities in vitro, its function in vivo remains unknown. Polκ is able to carry out TLS past benzo[a]pyrene (BaP) adducts in DNA (Rechkoblit et al., 2002; Suzuki et al., 2002; Zhang et al., 2002) and also past apurinic or apyrimidinic (AP) sites, acetylaminofluorene-DNA adducts (Ohashi et al., 2000b)