Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediates
NUCLEIC ACIDS RESEARCH, cilt.35, sa.12, ss.4103-4113, 2007 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 35 Sayı: 12
- Basım Tarihi: 2007
- Doi Numarası: 10.1093/nar/gkm404
- Dergi Adı: NUCLEIC ACIDS RESEARCH
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.4103-4113
- Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır
Özet
The Cockayne syndrome B (CSB) protein-defective in a majority of patients suffering from the rare autosomal disorder CS-is a member of the SWI2/SNF2 family with roles in DNA repair and transcription. We demonstrate herein that purified recombinant CSB and the major human apurinic/apyrimidinic (AP) endonuclease, APE1, physically and functionally interact. CSB stimulates the AP site incision activity of APE1 on normal (i.e. fully paired) and bubble AP-DNA substrates, with the latter being more pronounced ( =up to 6-fold). This activation is ATP-independent, and specific for the human CSB and full-length APE1 protein, as no CSB-dependent stimulation was observed with Escherichia coli endonuclease IV or an N-terminal truncated APE1 fragment. CSB and APE1 were also found in a common protein complex in human cell extracts, and recombinant CSB, when added back to CSB-deficient whole cell extracts, resulted in increased total AP site incision capacity. Moreover, human fibroblasts defective in CSB were found to be hypersensitive to both methyl methanesulfonate (MMS) and 5-hydroxymethyl 20-deoxyuridine, agents that introduce base excision repair (BER) DNA substrates/intermediates.