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PMID: 10823903 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A mechanistic basis for Mre11-directed DNA joining at microhomologies.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 12 ·2000-06-06 ·Pages 6409-14

Paull TT, Gellert M

Abstract

Repair of DNA double-strand breaks in vertebrate cells occurs mainly by an end-joining process that often generates junctions with sequence homologies of a few nucleotides. Mre11 is critical for this mode of repair in budding yeast and has been implicated in the microhomology-based joining. Here, we show that Mre11 exonuclease activity is sensitive to the presence of heterologous DNA, and to the structure and sequence of its ends. Addition of mismatched DNA ends stimulates degradation of DNA by Mre11, whereas cohesive ends strongly inhibit it. Furthermore, if a sequence identity is revealed during the course of degradation, it causes Mre11 nuclease activity to pause, thus stabilizing the junction at a site of microhomology. A nuclease-deficient Mre11 mutant that still binds DNA can also stimulate degradation by wild-type Mre11, suggesting that Mre11-DNA complexes may interact to bridge DNA ends and facilitate DNA joining.

MeSH Terms
Catalysis DNA/metabolism DNA Repair Endodeoxyribonucleases Exodeoxyribonucleases Exonucleases/physiology Fungal Proteins/physiology Saccharomyces cerevisiae Proteins
Chemicals
Fungal Proteins Saccharomyces cerevisiae Proteins DNA Endodeoxyribonucleases Exodeoxyribonucleases Exonucleases MRE11 protein, S cerevisiae
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Paull T T
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0540, USA.
Gellert M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.110144297
Published
2000-06-06
Pages
6409-14
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18616
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.110144297 PMC Full Text View journal details
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