Repair of damaged and mismatched DNA by the XPC homologues Rhp41 and Rhp42 of fission yeast.

نویسندگان

  • Thomas M Marti
  • Christophe Kunz
  • Oliver Fleck
چکیده

Rhp41 and Rhp42 of Schizosaccharomyces pombe are homologues of human XPC, which is involved in nucleotide excision repair (NER) of damaged DNA. Inactivation of rhp41 caused moderate sensitivity to ultraviolet (UV) radiation. In addition, an increase of mitotic mutation rates was observed in the rhp41 mutant, which was dependent on active translesion polymerase Z. UV sensitivity and mutation rates were not different between rhp42 and wild type, but compared to rhp41 were further increased in rhp41 rhp42 cells. Transcription of the fbp1 gene (induced in vegetative cells) and of the SPBC1289.14 gene (induced during meiosis) was strongly blocked by UV-induced damages in the rhp41 mutant, but not, or only slightly, reduced in rhp42 background. NER-dependent short-patch repair of mismatches formed during meiosis was slightly affected in rhp41, moderately affected in rhp42, and absent in rhp41 rhp42. Epistasis analysis with rhp7 and rhp26 indicates that Rhp41 and Rhp42 are both involved in the global genome and transcription-coupled repair subpathways of NER. Rhp41 plays a major role in damage repair and Rhp42 in mismatch repair.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Recognition of Damaged DNA for Nucleotide Excision Repair: A Correlated Motion Mechanism with a Mismatched cis-syn Thymine Dimer Lesion

Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575;...

متن کامل

Enhanced spontaneous DNA twisting/bending fluctuations unveiled by fluorescence lifetime distributions promote mismatch recognition by the Rad4 nucleotide excision repair complex

Rad4/XPC recognizes diverse DNA lesions including ultraviolet-photolesions and carcinogen-DNA adducts, initiating nucleotide excision repair. Studies have suggested that Rad4/XPC senses lesion-induced helix-destabilization to flip out nucleotides from damaged DNA sites. However, characterizing how DNA deformability and/or distortions impact recognition has been challenging. Here, using fluoresc...

متن کامل

RAD4 and RAD23/HMR Contribute to Arabidopsis UV Tolerance

In plants, exposure to solar ultraviolet (UV) light is unavoidable, resulting in DNA damage. Damaged DNA causes mutations, replication arrest, and cell death, thus efficient repair of the damaged DNA is essential. A light-independent DNA repair pathway called nucleotide excision repair (NER) is conserved throughout evolution. For example, the damaged DNA-binding protein Radiation sensitive 4 (R...

متن کامل

Kinetic gating mechanism of DNA damage recognition by Rad4/XPC

The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered R...

متن کامل

Roles of Rad23 protein in yeast nucleotide excision repair.

Nucleotide excision repair (NER) removes many different types of DNA lesions. Most NER proteins are indispensable for repair. In contrast, the yeast Rad23 represents a class of accessory NER proteins, without which NER activity is reduced but not eliminated. In mammals, the complex of HR23B (Rad23 homolog) and XPC (yeast Rad4 homolog) has been suggested to function in the damage recognition ste...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Genetics

دوره 164 2  شماره 

صفحات  -

تاریخ انتشار 2003