Open AccessDNA polymerase ζ cooperates with polymerases κ and ι in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients
Author(s) -
Omer Ziv,
Nicholas E. Geacintov,
Satoshi Nakajima,
Akira Yasui,
Zvi Livneh
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0812548106
Subject(s) - xeroderma pigmentosum , dna polymerase , polymerase , pyrimidine dimer , dna synthesis , dna polymerase ii , dna polymerase mu , nucleotide excision repair , dna repair , dna polymerase i , dna damage , microbiology and biotechnology , dna , biology , dna replication , chemistry , biochemistry , polymerase chain reaction , gene , reverse transcriptase , circular bacterial chromosome
Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out by DNA polymerase η, thePOLH gene product. A deficiency in DNA polymerase η due to germ-line mutations inPOLH causes the hereditary disease xeroderma pigmentosum variant (XPV ), which is characterized by sunlight sensitivity and extreme predisposition to sunlight-induced skin cancer.XPV cells are UV hypermutable due to the activity of mutagenic TLS across CPD, which explains the cancer predisposition of the patients. However, the identity of the backup polymerase that carries out this mutagenic TLS was unclear. Here, we show that DNA polymerase ζ cooperates with DNA polymerases κ and ι to carry out error-prone TLS across a TT CPD. Moreover, DNA polymerases ζ and κ, but not ι, protectXPV cells against UV cytotoxicity, independently of nucleotide excision repair. This presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load.