Complementation of aprataxin deficiency by base excision repair enzymes.

ABSTRACT: Abortive ligation during base excision repair (BER) leads to blocked repair intermediates containing a 5'-adenylated-deoxyribose phosphate (5'-AMP-dRP) group. Aprataxin (APTX) is able to remove the AMP group allowing repair to proceed. Earlier results had indicated that purified DNA polymerase ? (pol ?) removes the entire 5'-AMP-dRP group through its lyase activity and flap endonuclease 1 (FEN1) excises the 5'-AMP-dRP group along with one or two nucleotides. Here, using cell extracts from APTX-deficient cell lines, human Ataxia with Oculomotor Apraxia Type 1 (AOA1) and DT40 chicken B cell, we found that pol ? and FEN1 enzymatic activities were prominent and strong enough to complement APTX deficiency. In addition, pol ?, APTX and FEN1 coordinate with each other in processing of the 5'-adenylated dRP-containing BER intermediate. Finally, other DNA polymerases and a repair factor with dRP lyase activity (pol ?, pol ?, pol ? and Ku70) were found to remove the 5'-adenylated-dRP group from the BER intermediate. However, the activities of these enzymes were weak compared with those of pol ? and FEN1.

SUBMITTER: Caglayan M 

PROVIDER: S-EPMC4344515 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature