scholarly journals Role of polymerase β in complementing aprataxin deficiency during abasic-site base excision repair

2014 ◽  
Vol 21 (5) ◽  
pp. 497-499 ◽  
Author(s):  
Melike Çağlayan ◽  
Vinod K Batra ◽  
Akira Sassa ◽  
Rajendra Prasad ◽  
Samuel H Wilson
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Abasic Site ◽  
Base Excision

scholarly journals Damage sensor role of UV-DDB during base excision repair

2019 ◽  
Vol 26 (8) ◽  
pp. 695-703 ◽  
Author(s):  
Sunbok Jang ◽  
Namrata Kumar ◽  
Emily C. Beckwitt ◽  
Muwen Kong ◽  
Elise Fouquerel ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Base Excision

scholarly journals The Role of Base Excision Repair in the Sensitivity and Resistance to Temozolomide-Mediated Cell Death

2005 ◽  
Vol 65 (14) ◽  
pp. 6394-6400 ◽  
Author(s):  
Ram N. Trivedi ◽  
Karen H. Almeida ◽  
Jamie L. Fornsaglio ◽  
Sandra Schamus ◽  
Robert W. Sobol
Keyword(s):  
Cell Death ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Base Excision

scholarly journals MSH2–MSH6 stimulates DNA polymerase η, suggesting a role for A:T mutations in antibody genes

2005 ◽  
Vol 201 (4) ◽  
pp. 637-645 ◽  
Author(s):  
Teresa M. Wilson ◽  
Alexandra Vaisman ◽  
Stella A. Martomo ◽  
Patsa Sullivan ◽  
Li Lan ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Base Excision Repair ◽  
Somatic Hypermutation ◽  
Excision Repair ◽  
Cytidine Deaminase ◽  
Abasic Site ◽  
Cell Extracts ◽  
Activation Induced Cytidine Deaminase ◽  
Base Excision

Activation-induced cytidine deaminase deaminates cytosine to uracil (dU) in DNA, which leads to mutations at C:G basepairs in immunoglobulin genes during somatic hypermutation. The mechanism that generates mutations at A:T basepairs, however, remains unclear. It appears to require the MSH2–MSH6 mismatch repair heterodimer and DNA polymerase (pol) η, as mutations of A:T are decreased in mice and humans lacking these proteins. Here, we demonstrate that these proteins interact physically and functionally. First, we show that MSH2–MSH6 binds to a U:G mismatch but not to other DNA intermediates produced during base excision repair of dUs, including an abasic site and a deoxyribose phosphate group. Second, MSH2 binds to pol η in solution, and endogenous MSH2 associates with the pol in cell extracts. Third, MSH2–MSH6 stimulates the catalytic activity of pol η in vitro. These observations suggest that the interaction between MSH2–MSH6 and DNA pol η stimulates synthesis of mutations at bases located downstream of the initial dU lesion, including A:T pairs.

scholarly journals R-loops promote trinucleotide repeat deletion through DNA base excision repair enzymatic activities

2020 ◽  
Vol 295 (40) ◽  
pp. 13902-13913
Author(s):  
Eduardo E. Laverde ◽  
Yanhao Lai ◽  
Fenfei Leng ◽  
Lata Balakrishnan ◽  
Catherine H. Freudenreich ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Trinucleotide Repeat ◽  
Excision Repair ◽  
Enzymatic Activities ◽  
Cag Repeat ◽  
Abasic Site ◽  
Dna Damage And Repair ◽  
Dna Base Excision Repair ◽  
Treatment And Prevention ◽  
Base Excision

Trinucleotide repeat (TNR) expansion and deletion are responsible for over 40 neurodegenerative diseases and associated with cancer. TNRs can undergo somatic instability that is mediated by DNA damage and repair and gene transcription. Recent studies have pointed toward a role for R-loops in causing TNR expansion and deletion, and it has been shown that base excision repair (BER) can result in CAG repeat deletion from R-loops in yeast. However, it remains unknown how BER in R-loops can mediate TNR instability. In this study, using biochemical approaches, we examined BER enzymatic activities and their influence on TNR R-loops. We found that AP endonuclease 1 incised an abasic site on the nontemplate strand of a TNR R-loop, creating a double-flap intermediate containing an RNA:DNA hybrid that subsequently inhibited polymerase β (pol β) synthesis of TNRs. This stimulated flap endonuclease 1 (FEN1) cleavage of TNRs engaged in an R-loop. Moreover, we showed that FEN1 also efficiently cleaved the RNA strand, facilitating pol β loop/hairpin bypass synthesis and the resolution of TNR R-loops through BER. Consequently, this resulted in fewer TNRs synthesized by pol β than those removed by FEN1, thereby leading to repeat deletion. Our results indicate that TNR R-loops preferentially lead to repeat deletion during BER by disrupting the balance between the addition and removal of TNRs. Our discoveries open a new avenue for the treatment and prevention of repeat expansion diseases and cancer.

Sign in / Sign up

Export Citation Format

Share Document