XRCC1 interactions with base excision repair DNA intermediates.
Abasic (AP) sites in DNA arise either spontaneously, or through glycosylase-catalyzed excision of damaged bases. Their removal by the base excision repair (BER) pathway avoids their mutagenic and cytotoxic consequences. XRCC1 coordinates and facilitates single-strand break (SSB) repair and BER in mammalian cells. We report that XRCC1, through its NTD and BRCT1 domains, has affinity for several DNA intermediates in BER. As shown by its capacity to form a covalent complex via Schiff base, XRCC1 binds AP sites. APE1 suppresses binding of XRCC1 to unincised AP sites however, affinity was higher when the DNA carried an AP-lyase- or APE1-incised AP site. The AP site binding capacity of XRCC1 is enhanced by the presence of strand interruptions in the opposite strand. Binding of XRCC1 to BER DNA intermediates could play an important role to warrant the accurate repair of damaged bases, AP sites or SSBs, in particular in the context of clustered DNA damage.
Nazarkina
Zhanna K
ZK
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Prospect Lavrentieva 8, Novosibirsk 630090, Russia.
Khodyreva
Svetlana N
SN
Marsin
Stéphanie
S
Lavrik
Olga I
OI
Radicella
J Pablo
JP
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase