Slow repair of bulky DNA adducts along the nontranscribed strand of the human p53 gene may explain the strand bias of transversion mutations in cancers

Oncogene
M F DenissenkoM Tang

Abstract

Using UvrABC incision in combination with ligation-mediated PCR (LMPCR) we have previously shown that benzo(a)pyrene diol epoxide (BPDE) adduct formation along the nontranscribed strand of the human p53 gene is highly selective; the preferential binding sites coincide with the major mutation hotspots found in human lung cancers. Both sequence-dependent adduct formation and repair may contribute to these mutation hotspots in tumor tissues. To test this possibility, we have extended our previous studies by mapping the BPDE adduct distribution in the transcribed strand of the p53 gene and quantifying the rates of repair for individual damaged bases in exons 5, 7, and 8 for both DNA strands of this gene in normal human fibroblasts. We found that: (i) on both strands, BPDE adducts preferentially form at CpG sequences, and (ii) repair of BPDE adducts in the transcribed DNA strand is consistently faster than repair of adducts in the nontranscribed strand, while repair at the major damage hotspots (guanines at codons 157, 248 and 273) in the nontranscribed strand is two to four times slower than repair at other damage sites. These results strongly suggest that both preferential adduct formation and slow repair lead to hotspots for muta...Continue Reading

Citations

Aug 30, 2000·International Journal of Cancer. Journal International Du Cancer·C OstwaldM Barten
Aug 18, 2010·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Sanbao TangBin Zhou
Jun 6, 2000·Mutation Research·J EngelbergsM F Rajewsky
Jun 6, 2000·Mutation Research·G P Pfeifer
Oct 16, 2002·Mutation Research·Sergei N Rodin, Andrew S Rodin
Apr 26, 2003·Mutation Research·Gerd P Pfeifer, Pierre Hainaut
Apr 25, 2003·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Wei-Min GaoPhouthone Keohavong
Feb 18, 1999·Toxicology Letters·G P PfeiferM S Tang
Jan 22, 2005·Nature Reviews. Cancer·Andreas Luch
Mar 2, 2010·Médecine sciences : M/S·Sandrine LacosteRégen Drouin
May 18, 2000·Journal of the National Cancer Institute·L E SmithG P Pfeifer
Jun 19, 2003·Journal of the National Cancer Institute·Ahmad Besaratinia, Gerd P Pfeifer
Jul 9, 2004·Journal of the National Cancer Institute·Ahmad Besaratinia, Gerd P Pfeifer
May 23, 2003·Cold Spring Harbor Symposia on Quantitative Biology·P C HanawaltS Tornaletti
May 17, 2012·Cancer Research·Ian A PriorCarla Mattos
Sep 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Charles M RudinJonathan M Samet
Jun 25, 1998·Environmental Health Perspectives·T M Hernandez-Boussard, P Hainaut
Jun 27, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·V L Wilson
Aug 22, 2003·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Michael C Frühwald
Jan 15, 2011·Journal of Nucleic Acids·Bo Hang
Oct 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Zhaohui FengMoon-shong Tang
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·S N Rodin, A S Rodin
Nov 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tomoo OgiHaruo Ohmori
Nov 18, 2014·Current Opinion in Oncology·Gerd P Pfeifer

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.