DNA polymerase beta-dependent long patch base excision repair in living cells. 2010

Kenjiro Asagoshi, and Yuan Liu, and Aya Masaoka, and Li Lan, and Rajendra Prasad, and Julie K Horton, and Ashley R Brown, and Xiao-hong Wang, and Hussam M Bdour, and Robert W Sobol, and John-Stephen Taylor, and Akira Yasui, and Samuel H Wilson
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA.

We examined a role for DNA polymerase beta (Pol beta) in mammalian long patch base excision repair (LP BER). Although a role for Pol beta is well known in single-nucleotide BER, information on this enzyme in the context of LP BER has been limited. To examine the question of Pol beta involvement in LP BER, we made use of nucleotide excision repair-deficient human XPA cells expressing UVDE (XPA-UVDE), which introduces a nick directly 5' to the cyclobutane pyrimidine dimer or 6-4 photoproduct, leaving ends with 3'-OH and 5'-phosphorylated UV lesion. We observed recruitment of GFP-fused Pol beta to focal sites of nuclear UV irradiation, consistent with a role of Pol beta in repair of UV-induced photoproducts adjacent to a strand break. This was the first evidence of Pol beta recruitment in LP BER in vivo. In cell extract, a 5'-blocked oligodeoxynucleotide substrate containing a nicked 5'-cyclobutane pyrimidine dimer was repaired by Pol beta-dependent LP BER. We also demonstrated Pol beta involvement in LP BER by making use of mouse cells that are double null for XPA and Pol beta. These results were extended by experiments with oligodeoxynucleotide substrates and purified human Pol beta.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009841 Oligonucleotides Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed) Oligonucleotide
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011740 Pyrimidine Dimers Dimers found in DNA chains damaged by ULTRAVIOLET RAYS. They consist of two adjacent PYRIMIDINE NUCLEOTIDES, usually THYMINE nucleotides, in which the pyrimidine residues are covalently joined by a cyclobutane ring. These dimers block DNA REPLICATION. Cyclobutane Pyrimidine Dimer,Cyclobutane-Pyrimidine Dimer,Cytosine-Thymine Dimer,Pyrimidine Dimer,Thymine Dimer,Thymine Dimers,Cyclobutane-Pyrimidine Dimers,Cytosine-Thymine Dimers,Thymine-Cyclobutane Dimer,Thymine-Thymine Cyclobutane Dimer,Cyclobutane Dimer, Thymine-Thymine,Cyclobutane Dimers, Thymine-Thymine,Cyclobutane Pyrimidine Dimers,Cytosine Thymine Dimer,Cytosine Thymine Dimers,Pyrimidine Dimer, Cyclobutane,Pyrimidine Dimers, Cyclobutane,Thymine Cyclobutane Dimer,Thymine Thymine Cyclobutane Dimer,Thymine-Cyclobutane Dimers,Thymine-Thymine Cyclobutane Dimers
D002457 Cell Extracts Preparations of cell constituents or subcellular materials, isolates, or substances. Cell Extract,Extract, Cell,Extracts, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004720 Endonucleases Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. Endonuclease
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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