Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning

Molecular Cell
K SugasawaF Hanaoka

Abstract

For mammalian nucleotide excision repair (NER), DNA lesions are recognized in at least two steps involving detection of unpaired bases by the XPC protein complex and the subsequent verification of injured bases. Although lesion verification is important to ensure high damage discrimination and the accuracy of the repair system, it has been unclear how this is accomplished. Here, we show that damage verification involves scanning of a DNA strand from the site where XPC is initially bound. Translocation by the NER machinery exhibits a 5'-to-3' directionality, strongly suggesting involvement of the XPD helicase, a component of TFIIH. Furthermore, the initial orientation of XPC binding is crucial in that only one DNA strand is selected to search for the presence of lesions. Our results dissect the intricate molecular mechanism of NER and provide insights into a strategy for mammalian cells to survey large genomes to detect DNA damage.

References

Jun 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·E Y Oh, L Grossman
Feb 24, 1995·The Journal of Biological Chemistry·T MatsudaF Hanaoka
Dec 1, 1996·Nucleic Acids Research·M SaijoK Tanaka
Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·M T HessH Naegeli
Apr 24, 1999·Biochimie·S Tornaletti, P C Hanawalt
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·N Buschta-HedayatH Naegeli
Jul 3, 1999·The Journal of Biological Chemistry·Y FujiwaraS Iwai
Feb 8, 2000·The Journal of Biological Chemistry·G S WinklerG Weeda
May 18, 2001·Nature·J H Hoeijmakers
Aug 21, 2001·Molecular Cell·M VolkerL H Mullenders
Feb 2, 2002·Nature Reviews. Molecular Cell Biology·Jesper Q Svejstrup
Mar 20, 2002·Nature Reviews. Cancer·E C Friedberg
Aug 29, 2003·The Journal of Biological Chemistry·Maureen E FitchJames M Ford
Oct 1, 2003·The EMBO Journal·Thilo RiedlJean-Marc Egly
Feb 9, 2006·Chemical Reviews·Ludovic C J Gillet, Orlando D Schärer
Sep 21, 2007·Nature·Jung-Hyun Min, Nikola P Pavletich
Jul 11, 2008·Molecular Cell·Frédéric CoinJean Marc Egly

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Citations

Nov 10, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Emilie WarrickThierry Magnaldo
May 11, 2012·Nature Reviews. Molecular Cell Biology·Emmanuel Compe, Jean-Marc Egly
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nadine MathieuHanspeter Naegeli
Apr 24, 2013·Nucleic Acids Research·Alexey EvdokimovOlga Lavrik
Oct 29, 2010·Cold Spring Harbor Perspectives in Biology·Giuseppina Giglia-MariWim Vermeulen
Jul 7, 2011·Molecular and Cellular Biology·Arjan F TheilGiuseppina Giglia-Mari
May 17, 2011·Biochemistry. Biokhimii︠a︡·N I RechkunovaO I Lavrik
Oct 31, 2012·International Journal of Molecular Sciences·Mariona TerradasAnna Genescà
Feb 21, 2014·Proceedings of the National Academy of Sciences of the United States of America·Nia M HainesNigel J Savery
Aug 31, 2010·Cellular and Molecular Life Sciences : CMLS·Almass-Houd Aguissa-TouréGang Li
Mar 21, 2012·The Journal of Cell Biology·Steven BerginkWim Vermeulen
Nov 2, 2015·Cellular and Molecular Life Sciences : CMLS·Marjo-Riitta PuumalainenHanspeter Naegeli
Jun 21, 2011·DNA Repair·Hanspeter Naegeli, Kaoru Sugasawa
May 20, 2011·DNA Repair·Adebanke F FagbemiOrlando D Schärer
Apr 7, 2011·Mechanisms of Ageing and Development·Thierry Nouspikel
Jun 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sandra C KochThomas Carell
Oct 1, 2015·DNA Repair·Leah NemzowFeng Gong
Nov 18, 2011·Molecular Biology International·Hannes Lans, Wim Vermeulen
May 12, 2010·Journal of Cellular Physiology·Liren LiuPengbo Zhou
Nov 28, 2013·Journal of Molecular Recognition : JMR·Claudia N Buechner, Ingrid Tessmer
Jul 27, 2010·Environmental and Molecular Mutagenesis·Richard D Wood
May 21, 2013·DNA Repair·Teruaki Iyama, David M Wilson
Jul 15, 2015·DNA Repair·Irfan KhanRobert M Brosh
Jul 27, 2014·Experimental Cell Research·Loes van CuijkJurgen A Marteijn
Jul 8, 2015·Nature Communications·Loes van CuijkJurgen A Marteijn
Feb 16, 2015·Cellular and Molecular Life Sciences : CMLS·Sergey Alekseev, Frédéric Coin
Feb 9, 2013·Current Biology : CB·Maria Spies
Nov 19, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Caroline Olivieri da Silva FrozzaMariana Roesch-Ely
May 21, 2016·Frontiers in Genetics·Peter RüthemannHanspeter Naegeli

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