5. DNA polymerase eta

DNA polymerase (Pol ) is the only one of the fifteen human DNA-dependent DNA polymerases for which a natural occurring deficiency is known to predispose humans to cancer. Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder, associated with a greatly increased risk of sunlightinduced skin tumors, and individuals with the variant type of this syndrome, XP-V, have defects in Pol . Pol has a DNA polymerase activity capable of catalyzing translesion DNA synthesis past the most prominent UV-induced lesion, a cis-syn TT-cyclobutane pyrimidine dimer (CPD), with high efficiency and fidelity. Crystal structure of human Pol complexed with CPDcontaining template-primer DNA reveals that Pol is the DNA polymerase for bypassing CPD lesion. In addition, mammalian Pol has other physiological functions including somatic hypermutation, homologous recombination and replication of common fragile sites. Pol recruitment is regulated by monoubiquitination and de-ubiquitination of PCNA at least in part. Correspondence/Reprint request: Dr. Fumio Hanaoka, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan. E-mail: [email protected] Chikahide Masutani et al. 74