Journal article
Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration
Nature (London), Vol.502(7471), pp.393-396
10/17/2013
DOI: 10.1038/nature12585
PMCID: PMC3915060
PMID: 24025768
Abstract
During DNA repair by homologous recombination (HR), DNA synthesis copies information from a template DNA molecule. Multiple DNA polymerases have been implicated in repair-specific DNA synthesis
1
–
3
, but it has remained unclear whether a DNA helicase is involved in this reaction. A good candidate is Pif1, an evolutionarily conserved helicase in
S. cerevisiae
important for break-induced replication (BIR)
4
as well as HR-dependent telomere maintenance in the absence of telomerase
5
found in 10–15% of all cancers
6
. Pif1 plays a role in DNA synthesis across hard-to-replicate sites
7
,
8
and in lagging strand synthesis with Polδ
9
–
11
. Here we provide evidence that Pif1 stimulates DNA synthesis during BIR and crossover recombination. The initial steps of BIR occur normally in Pif1-deficient cells, but Polδ recruitment and DNA synthesis are decreased, resulting in premature resolution of DNA intermediates into half crossovers. Purified Pif1 protein strongly stimulates Polδ-mediated DNA synthesis from a D-loop made by the Rad51 recombinase. Importantly, Pif1 liberates the newly synthesized strand to prevent the accumulation of topological constraint and to facilitate extensive DNA synthesis via the establishment of a migrating D-loop structure. Our results uncover a novel function of Pif1 and provide insights into the mechanism of HR.
Details
- Title: Subtitle
- Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration
- Creators
- Marenda A Wilson - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324YoungHo Kwon - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Yuanyuan Xu - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Woo-Hyun Chung - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Peter Chi - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Hengyao Niu - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Ryan Mayle - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Xuefeng Chen - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Anna Malkova - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Patrick Sung - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324Grzegorz Ira - Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, TX 77030 Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea Institute of Biochemical Sciences, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan; Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202 Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242-1324
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.502(7471), pp.393-396
- DOI
- 10.1038/nature12585
- PMID
- 24025768
- PMCID
- PMC3915060
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 10/17/2013
- Academic Unit
- Biology
- Record Identifier
- 9984217429702771
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