Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in Tumorigenesis

Jason A. Lehman, Lindsey Mayo

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and hyperactivation of oncogenes. One such oncogenic protein product is the murine double-minute 2, or Mdm2. While, Mdm2 has been primarily associated as the negative regulator of the p53 tumor suppressor protein there are many p53-independent roles demonstrated for this oncogene. DNA damage and chemotherapeutic agents are known to activate Mdm2 and DNA repair pathways. There are five primary DNA repair pathways involved in the maintenance of genomic integrity: Nucleotide excision repair (NER), Base excision repair (BER), Mismatch repair (MMR), Non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we will briefly describe these pathways and also delineate the functional interaction of Mdm2 with multiple DNA repair proteins. We will illustrate the importance of these interactions with Mdm2 and discuss how this is important for tumor progression, cellular proliferation in cancer.

Original languageEnglish
Pages (from-to)16373-16386
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume13
Issue number12
DOIs
StatePublished - 2012

Fingerprint

DNA Repair
DNA Damage
tumor suppressor proteins
Carcinogenesis
DNA
Repair
deoxyribonucleic acid
oncogenes
damage
Proteins
Tumors
Oncogenes
cancer
proteins
regulators
nucleotides
Tumor Suppressor Proteins
Tumor Suppressor Protein p53
Neoplasms
DNA Mismatch Repair

Keywords

  • Base excision repair
  • Cancer
  • Homologous recombination
  • Mismatch repair
  • Murine double minute-2
  • Non-homologous end joining
  • Nucleotide excision repair

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)

Cite this

Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in Tumorigenesis. / Lehman, Jason A.; Mayo, Lindsey.

In: International Journal of Molecular Sciences, Vol. 13, No. 12, 2012, p. 16373-16386.

Research output: Contribution to journalArticle

@article{6a124140299c48d199d5b965e261312c,
title = "Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in Tumorigenesis",
abstract = "The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and hyperactivation of oncogenes. One such oncogenic protein product is the murine double-minute 2, or Mdm2. While, Mdm2 has been primarily associated as the negative regulator of the p53 tumor suppressor protein there are many p53-independent roles demonstrated for this oncogene. DNA damage and chemotherapeutic agents are known to activate Mdm2 and DNA repair pathways. There are five primary DNA repair pathways involved in the maintenance of genomic integrity: Nucleotide excision repair (NER), Base excision repair (BER), Mismatch repair (MMR), Non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we will briefly describe these pathways and also delineate the functional interaction of Mdm2 with multiple DNA repair proteins. We will illustrate the importance of these interactions with Mdm2 and discuss how this is important for tumor progression, cellular proliferation in cancer.",
keywords = "Base excision repair, Cancer, Homologous recombination, Mismatch repair, Murine double minute-2, Non-homologous end joining, Nucleotide excision repair",
author = "Lehman, {Jason A.} and Lindsey Mayo",
year = "2012",
doi = "10.3390/ijms131216373",
language = "English",
volume = "13",
pages = "16373--16386",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "12",

}

TY - JOUR

T1 - Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in Tumorigenesis

AU - Lehman, Jason A.

AU - Mayo, Lindsey

PY - 2012

Y1 - 2012

N2 - The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and hyperactivation of oncogenes. One such oncogenic protein product is the murine double-minute 2, or Mdm2. While, Mdm2 has been primarily associated as the negative regulator of the p53 tumor suppressor protein there are many p53-independent roles demonstrated for this oncogene. DNA damage and chemotherapeutic agents are known to activate Mdm2 and DNA repair pathways. There are five primary DNA repair pathways involved in the maintenance of genomic integrity: Nucleotide excision repair (NER), Base excision repair (BER), Mismatch repair (MMR), Non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we will briefly describe these pathways and also delineate the functional interaction of Mdm2 with multiple DNA repair proteins. We will illustrate the importance of these interactions with Mdm2 and discuss how this is important for tumor progression, cellular proliferation in cancer.

AB - The alteration of tumorigenic pathways leading to cancer is a degenerative disease process typically involving inactivation of tumor suppressor proteins and hyperactivation of oncogenes. One such oncogenic protein product is the murine double-minute 2, or Mdm2. While, Mdm2 has been primarily associated as the negative regulator of the p53 tumor suppressor protein there are many p53-independent roles demonstrated for this oncogene. DNA damage and chemotherapeutic agents are known to activate Mdm2 and DNA repair pathways. There are five primary DNA repair pathways involved in the maintenance of genomic integrity: Nucleotide excision repair (NER), Base excision repair (BER), Mismatch repair (MMR), Non-homologous end joining (NHEJ) and homologous recombination (HR). In this review, we will briefly describe these pathways and also delineate the functional interaction of Mdm2 with multiple DNA repair proteins. We will illustrate the importance of these interactions with Mdm2 and discuss how this is important for tumor progression, cellular proliferation in cancer.

KW - Base excision repair

KW - Cancer

KW - Homologous recombination

KW - Mismatch repair

KW - Murine double minute-2

KW - Non-homologous end joining

KW - Nucleotide excision repair

UR - http://www.scopus.com/inward/record.url?scp=84871688244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871688244&partnerID=8YFLogxK

U2 - 10.3390/ijms131216373

DO - 10.3390/ijms131216373

M3 - Article

VL - 13

SP - 16373

EP - 16386

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 12

ER -