Publication Date:
2013-09-13
Description:
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, but it has remained unclear whether a DNA helicase is involved in this reaction. A good candidate DNA helicase is Pif1, an evolutionarily conserved helicase in Saccharomyces cerevisiae important for break-induced replication (BIR) as well as HR-dependent telomere maintenance in the absence of telomerase found in 10-15% of all cancers. Pif1 has a role in DNA synthesis across hard-to-replicate sites and in lagging-strand synthesis with polymerase delta (Poldelta). 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 Poldelta recruitment and DNA synthesis are decreased, resulting in premature resolution of DNA intermediates into half-crossovers. Purified Pif1 protein strongly stimulates Poldelta-mediated DNA synthesis from a D-loop made by the Rad51 recombinase. Notably, 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915060/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915060/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Marenda A -- Kwon, YoungHo -- Xu, Yuanyuan -- Chung, Woo-Hyun -- Chi, Peter -- Niu, Hengyao -- Mayle, Ryan -- Chen, Xuefeng -- Malkova, Anna -- Sung, Patrick -- Ira, Grzegorz -- ES007061/ES/NIEHS NIH HHS/ -- ES015632/ES/NIEHS NIH HHS/ -- GM057814/GM/NIGMS NIH HHS/ -- GM080600/GM/NIGMS NIH HHS/ -- GM084242/GM/NIGMS NIH HHS/ -- R01 ES007061/ES/NIEHS NIH HHS/ -- R01 ES015632/ES/NIEHS NIH HHS/ -- R01 GM057814/GM/NIGMS NIH HHS/ -- R01 GM080600/GM/NIGMS NIH HHS/ -- R01 GM084242/GM/NIGMS NIH HHS/ -- R03 ES016434/ES/NIEHS NIH HHS/ -- T32 GM008307/GM/NIGMS NIH HHS/ -- T32GM07526-34/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Oct 17;502(7471):393-6. doi: 10.1038/nature12585. Epub 2013 Sep 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baylor College of Medicine, Department of Molecular & Human Genetics, One Baylor Plaza, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24025768" target="_blank"〉PubMed〈/a〉
Keywords:
*Crossing Over, Genetic
;
DNA Helicases/deficiency/genetics/*metabolism
;
DNA Polymerase III/*metabolism
;
DNA Repair
;
*DNA Replication
;
DNA, Fungal/*biosynthesis/chemistry/metabolism
;
Nucleic Acid Conformation
;
Rad51 Recombinase/metabolism
;
Saccharomyces cerevisiae/*enzymology/*genetics/metabolism
;
Saccharomyces cerevisiae Proteins/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
