DNA polymerase Β is critical for mouse meiotic synapsis Journal Article

Authors: Kidane, D.; Jonason, A. S.; Gorton, T. S.; Mihaylov, I.; Pan, J.; Keeney, S.; De Rooij, D. G.; Ashley, T.; Keh, A.; Liu, Y.; Banerjee, U.; Zelterman, D.; Sweasy, J. B.
Article Title: DNA polymerase Β is critical for mouse meiotic synapsis
Abstract: We have shown earlier that DNA polymerase Β (Pol Β) localizes to the synaptonemal complex (SC) during Prophase I of meiosis in mice. Pol Β localizes to synapsed axes during zygonema and pachynema, and it associates with the ends of bivalents during late pachynema and diplonema. To test whether these localization patterns reflect a function for Pol Β in recombination and/or synapsis, we used conditional gene targeting to delete the PolB gene from germ cells. We find that Pol Β-deficient spermatocytes are defective in meiotic chromosome synapsis and undergo apoptosis during Prophase I. We also find that SPO11-dependent γH2AX persists on meiotic chromatin, indicating that Pol Β is critical for the repair of SPO11-induced double-strand breaks (DSBs). Pol Β-deficient spermatocytes yielded reduced steady-state levels of the SPO11-oligonucleotide complexes that are formed when SPO11 is removed from the ends of DSBs, and cytological experiments revealed that chromosome-associated foci of replication protein A (RPA), RAD51 and DMC1 are less abundant in Pol Β-deficient spermatocyte nuclei. Localization of Pol Β to meiotic chromosomes requires the formation of SPO11-dependent DSBs. Taken together, these findings strongly indicate that Pol Β is required at a very early step in the processing of meiotic DSBs, at or before the removal of SPO11 from DSB ends and the generation of the 3′ single-stranded tails necessary for subsequent strand exchange. The chromosome synapsis defects and Prophase I apoptosis of Pol Β-deficient spermatocytes are likely a direct consequence of these recombination defects. © 2010 European Molecular Biology Organization.
Keywords: controlled study; unclassified drug; gene deletion; nonhuman; dna polymerase; animal cell; mouse; pachytene; spermatocyte; synaptonemal complex; meiosis; animals; mice; spermatocytes; animal tissue; gene targeting; mus; dna repair; apoptosis; germ cell; animal experiment; dna strand breakage; chromatin; dna breaks, double-stranded; replication factor a; single stranded dna; oligonucleotide; chromosome pairing; synapsis; histone h2ax; chromosomes; gene location; rad51 protein; spo11 protein; esterases; dna polymerase beta; prophase; dna directed dna polymerase beta; histone h2ax gamma; pol beta gene; structural gene; seminiferous tubules; diplonema
Journal Title: EMBO Journal
Volume: 29
Issue: 2
ISSN: 0261-4189
Publisher: Wiley Blackwell  
Date Published: 2010-01-20
Start Page: 410
End Page: 423
Language: English
DOI: 10.1038/emboj.2009.357
PUBMED: 20019666
PROVIDER: scopus
PMCID: PMC2824467
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: EMJOD" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Scott N Keeney
    113 Keeney
  2. Jing Pan
    7 Pan