Telomeric D-loops containing 8-oxo-2'-deoxyguanosine are preferred substrates for Werner and Bloom syndrome helicases and are bound by POT1.
8-Oxo-2'-deoxyguanosine (8-oxodG) is one of the most important oxidative DNA lesions, and G-rich telomeric DNA is especially susceptible to oxidative DNA damage. RecQ helicases WRN and BLM and telomere-binding protein POT1 are thought to play roles in telomere maintenance. This study examines the ability of WRN, BLM, and RecQ5 to unwind and POT1 to bind telomeric D-loops containing 8-oxodG. The results demonstrate that WRN and BLM preferentially unwind telomeric D-loops containing 8-oxodG and that POT1 binds with higher affinity to telomeric D-loops with 8-oxodG but shows no preference for telomeric single-stranded DNA with 8-oxodG. We speculate that telomeric D-loops with 8-oxodG may have a greater tendency to form G-quadruplex DNA structures than telomeric DNA lacking 8-oxodG.
Ghosh
Avik
A
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.
Rossi
Marie L
ML
Aulds
Jason
J
Croteau
Deborah
D
Bohr
Vilhelm A
VA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D053484:RecQ Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000089804:Shelterin Complex; D013379:Substrate Specificity; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005090:Exodeoxyribonucleases; C097151:Bloom syndrome protein; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D003849:Deoxyguanosine