p53 and p21 Regulate Error-Prone DNA Repair to Yield a Lower Mutation Load

Sharon Avkin, Ziv Sevilya, Leanne Toube, Nicholas Geacintov, Stephen G. Chaney, Moshe Oren, Zvi Livneh

Research output: Contribution to journalArticle

Abstract

Regulation of mutation rates is critical for maintaining genome stability and controlling cancer risk. A special challenge to this regulation is the presence of multiple mutagenic DNA polymerases in mammals. These polymerases function in translesion DNA synthesis (TLS), an error-prone DNA repair process that involves DNA synthesis across DNA lesions. We found that in mammalian cells TLS is controlled by the tumor suppressor p53, and by the cell cycle inhibitor p21 via its PCNA-interacting domain, to maintain a low mutagenic load at the price of reduced repair efficiency. This regulation may be mediated by binding of p21 to PCNA and via DNA damage-induced ubiquitination of PCNA, which is stimulated by p53 and p21. Loss of this regulation by inactivation of p53 or p21 causes an out of control lesion-bypass activity, which increases the mutational load and might therefore play a role in pathogenic processes caused by genetic instability.

Original languageEnglish (US)
Pages (from-to)407-413
Number of pages7
JournalMolecular Cell
Volume22
Issue number3
DOIs
StatePublished - May 5 2006

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DNA Repair
Proliferating Cell Nuclear Antigen
Mutation
DNA
Genetic Phenomena
Genomic Instability
Ubiquitination
Mutation Rate
DNA-Directed DNA Polymerase
DNA Damage
Mammals
Neoplasms
Cell Cycle

Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Avkin, S., Sevilya, Z., Toube, L., Geacintov, N., Chaney, S. G., Oren, M., & Livneh, Z. (2006). p53 and p21 Regulate Error-Prone DNA Repair to Yield a Lower Mutation Load. Molecular Cell, 22(3), 407-413. https://doi.org/10.1016/j.molcel.2006.03.022

p53 and p21 Regulate Error-Prone DNA Repair to Yield a Lower Mutation Load. / Avkin, Sharon; Sevilya, Ziv; Toube, Leanne; Geacintov, Nicholas; Chaney, Stephen G.; Oren, Moshe; Livneh, Zvi.

In: Molecular Cell, Vol. 22, No. 3, 05.05.2006, p. 407-413.

Research output: Contribution to journalArticle

Avkin, S, Sevilya, Z, Toube, L, Geacintov, N, Chaney, SG, Oren, M & Livneh, Z 2006, 'p53 and p21 Regulate Error-Prone DNA Repair to Yield a Lower Mutation Load', Molecular Cell, vol. 22, no. 3, pp. 407-413. https://doi.org/10.1016/j.molcel.2006.03.022
Avkin, Sharon ; Sevilya, Ziv ; Toube, Leanne ; Geacintov, Nicholas ; Chaney, Stephen G. ; Oren, Moshe ; Livneh, Zvi. / p53 and p21 Regulate Error-Prone DNA Repair to Yield a Lower Mutation Load. In: Molecular Cell. 2006 ; Vol. 22, No. 3. pp. 407-413.
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