Xeroderma Pigmentosum Variant: From a Human Genetic Disorder to a Novel DNA Polymerase (original) (raw)

  1. C. MASUTANI,
  2. R. KUSUMOTO,
  3. A. YAMADA,
  4. M. YUASA,
  5. M. ARAKI,
  6. T. NOGIMORI,
  7. M. YOKOI,
  8. T. EKI,
  9. S. IWAI, and
  10. F. HANAOKA
  11. *Institute for Molecular and Cellular Biology, Osaka University and CREST, Japan Science and Technology Corporation, 1-3 Yamada-oka; † The Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871; ‡ RIKEN (The Institute of Physical and Chemical Research), Wako-shi, Saitama 351-0198; §Biomolecular Engineering Research Institute, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan

Excerpt

DNA replication in eukaryotic cells is a complex process requiring a variety of proteins to synthesize the leading and lagging strands of DNA in an asymmetric and coordinated manner (Bambara et al. 1997; Waga andStillman 1998). A myriad of lesions in DNA are causedby ubiquitous environmental and endogenous genotoxicagents. These lesions can interfere with normal DNAmetabolism including DNA replication, eventually resulting in mutations that lead to carcinogenesis and/orcell death. To maintain the integrity of the genetic material, cells possess multiple pathways including checkpoint mechanisms in various phases of cell cycle and repair mechanisms such as nucleotide excision and baseexcision repair pathways (Friedberg et al. 1995). However, not all lesions on the genome can be repaired efficiently by these processes in time for DNA replication,and some types of lesions are repaired very inefficiently.To prevent acute cell death through arrested DNA replication at unrepaired lesions, cells acquired a variety ofmechanisms to avoid interference of replication at the lesions so-called postreplication repair during evolution(Friedberg et al. 1995)...