hMYH cell cycle-dependent expression, subcellular localization and association with replication foci: Evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs

Istvan Boldogh, Daun Milligan, Myung Soog Lee, Heather Bassett, R. Stephen Lloyd, Amanda K. McCullough

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

The human MutY homolog, hMYH, is an adenine-specific DNA glycosylase that removes adenines or 2-hydroxyadenines mispaired with guanines or 8-oxoguanines. In order to prevent mutations, this activity must be directed to the newly synthesized strand and not the template strand during DNA synthesis. The subcellular localization and expression of hMYH has been studied in serum-stimulated, proliferating MRC5 cells. Using specific antibodies, we demonstrate that endogenous hMYH protein localized both to nuclei and mitochondria. hMYH in the nuclei is distinctly distributed and co-localized with BrdU at replication foci and with proliferating cell nuclear antigen (PCNA). The levels of hMYH in the nucleus increased 3- to 4-fold during progression of the cell cycle and reached maximum levels in S phase compared to early G1. Similar results were obtained for PCNA, while there were no notable changes in expression of 8-oxoguanine glycosylase or the human MutT homolog, MTH1, throughout the cell cycle. The cell cycle-dependent expression and localization of hMYH at sites of DNA replication suggest a role for this glycosylase in immediate post-replication DNA base excision repair.

Original languageEnglish (US)
Pages (from-to)2802-2809
Number of pages8
JournalNucleic Acids Research
Volume29
Issue number13
StatePublished - Jul 1 2001

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Adenine
Cell Cycle
Proliferating Cell Nuclear Antigen
DNA Replication
DNA Glycosylases
Guanine
Bromodeoxyuridine
S Phase
DNA Repair
Mitochondria
Mutation
Antibodies
DNA
Serum
8-hydroxyguanine
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

hMYH cell cycle-dependent expression, subcellular localization and association with replication foci : Evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs. / Boldogh, Istvan; Milligan, Daun; Lee, Myung Soog; Bassett, Heather; Lloyd, R. Stephen; McCullough, Amanda K.

In: Nucleic Acids Research, Vol. 29, No. 13, 01.07.2001, p. 2802-2809.

Research output: Contribution to journalArticle

Boldogh, Istvan ; Milligan, Daun ; Lee, Myung Soog ; Bassett, Heather ; Lloyd, R. Stephen ; McCullough, Amanda K. / hMYH cell cycle-dependent expression, subcellular localization and association with replication foci : Evidence suggesting replication-coupled repair of adenine:8-oxoguanine mispairs. In: Nucleic Acids Research. 2001 ; Vol. 29, No. 13. pp. 2802-2809.
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