p21(waf1/cip1)-null human fibroblasts are deficient in nucleotide excision repair downstream the recruitment of PCNA to DNA repair sites

Oncogene
Lucia A StivalaEnnio Prosperi

Abstract

The cyclin-dependent kinase inhibitor p21(waf1/cip1) is known to impair DNA synthesis by binding to PCNA, the co-factor of DNA polymerases delta and epsilon. However, a positive role for p21 in nucleotide excision repair (NER) has been suggested. In this study, the sensitivity to DNA damage and DNA repair efficiency were investigated in p21-null human fibroblasts obtained by targeted homologous recombination. After UV-C irradiation, p21-/- cells showed a threefold reduction in clonogenic survival and an increased susceptibility to apoptosis, as compared with parental p21+/+ cells. Removal of cyclobutane pyrimidine dimers was significantly reduced in p21-/- cells both in the whole genome, and at the level of the rDNA gene cluster, as determined by immunoassay and Southern blot, respectively. After DNA damage, the recruitment of PCNA as detergent-insoluble form associated to DNA repair sites in p21-/- fibroblasts, was comparable to that observed in parental p21+/+ cells. However, PCNA remained associated with DNA for a longer period in p21-/- than in p21+/+ cells. These results suggest that in human cells, p21 is required for NER at a step located downstream the recruitment of PCNA to DNA repair sites.

References

Jul 11, 1992·Nucleic Acids Research·A F Nichols, A Sancar
Feb 1, 1990·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D L Mitchell, P S Hartman
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·J M Ford, P C Hanawalt
Sep 15, 1995·The Journal of Biological Chemistry·Z Q PanJ Hurwitz
Dec 1, 1994·Current Biology : CB·M K ShivjiJ J Blow
Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·H Flores-RozasJ Hurwitz
Dec 16, 1994·Science·L H Hartwell, M B Kastan
Jun 1, 1994·Journal of Photochemistry and Photobiology. B, Biology·A A VinkL Roza
Oct 5, 1993·Biochemistry·F C Christians, P C Hanawalt
May 31, 1996·The Journal of Biological Chemistry·L K FritzM J Smerdon
Sep 1, 1996·Molecular and Cellular Biology·J ChenA Dutta
Jan 1, 1996·Annual Review of Biochemistry·R D Wood
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·U ChenA Dutta
Apr 1, 1997·Carcinogenesis·R D Wood, M K Shivji
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·D S LevinA E Tomkinson
Dec 12, 1997·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Z O Jónsson, U Hübscher
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·B J HwangG Chu
Jul 1, 1999·Genes & Development·C J Sherr, J M Roberts
Jul 9, 1999·Molecular Biology of the Cell·M P CooperV A Bohr

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Citations

Jun 1, 2005·Biochimica Et Biophysica Acta·Leena Latonen, Marikki Laiho
Aug 6, 2000·Oral Oncology·K Harada, G R Ogden
Nov 16, 2013·International Journal of Molecular Sciences·Razmik MirzayansDavid Murray
Nov 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wensheng WangRobert A Bambara
Aug 23, 2002·The Journal of Investigative Dermatology·Tomoko MaedaVictor A Tron
Mar 15, 2008·Leukemia Research·Benigno C ValdezBorje S Andersson
Jun 3, 2006·Journal of Cellular Physiology·Luciana E Giono, James J Manfredi
Jan 27, 2015·Archives of Toxicology·Daniel Speidel
Aug 22, 2003·The Journal of Biological Chemistry·Isabelle FrouinA Ivana Scovassi
Jan 10, 2002·The Journal of Biological Chemistry·Lothar RössigStefanie Dimmeler
Feb 6, 2020·International Journal of Molecular Sciences·Sylwia PietrasikJanusz Blasiak
Feb 7, 2021·Journal of Cancer Research and Clinical Oncology·Yanbei KuangQiang Li
Feb 9, 2006·Chemical Reviews·Marie L RossiRobert A Bambara

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