4ce40b556e9ce5849d44288de6044551 pmc_9456223.pdf d11155eb49eb1da086227e222239f98519ef578d pmc_9456223.pdf ca64727a553776ecd1eea35c369955f664ac7157e40af78f577288130dde543c pmc_9456223.pdf Title: p53 Controls Meiotic Prophase Progression and Crossover Formation Subject: Meiosis initiates with the formation of double strand breaks (DSBs) throughout the genome. To avoid genomic instability, these DSBs need to be correctly repaired by homologous recombination. Surveillance mechanisms involving the DNA damage response (DDR) pathway ATM-CHK2-p53 can detect the persistence of unrepaired DBSs and activate the recombination-dependent arrest at the pachytene stage. However, a complete understanding of p53 functions under normal physiological conditions remains lacking. Here, we report a detailed analysis of the p53 role during meiotic prophase in mice spermatocytes. We show that the absence of p53 regulates prophase progression by slowing down the pachytene stage when the recombination-dependent arrest occurs. Furthermore, our results show that p53 is necessary for proper crossover (CO) formation and localization. Our study contributes to a deeper understanding of p53 roles during the meiotic prophase. Keywords: p53; meiosis; synaptonemal complex; DSB repair; H2AX; crossover; MLH1 Author: Marina Marcet-Ortega, Andros Maldonado-Linares, Maria López-Panadés and Ignasi Roig Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Aug 31 09:55:47 2022 CEST ModDate: Wed Aug 31 10:06:23 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2141263 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HJOMHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 QRADTQ+VnURWPalladioL Type 1 Custom yes yes no 15 0 MDJLZU+EURM10 Type 1 Builtin yes yes no 19 0 HKXTER+URWPalladioL-Bold Type 1 Custom yes yes no 23 0 THXLZB+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 TTBNAG+URWPalladioL-Ital Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 50 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 YFFKLH+CMSY10 Type 1 Builtin yes yes no 75 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 87 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 91 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 95 0 BCDJEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 99 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 118 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 122 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 126 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 130 0 BCDJEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 137 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 156 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 160 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 164 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 168 0 BCDJEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 175 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 192 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 196 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 200 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 204 0 BCDJEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 211 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-28 02:27:49 CEST RepresentationInformation: pmc_9456223.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-09-23 02:14:50 CEST Size: 2141263 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 433 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Testis Size in p53-/- Mutant Mice Is Not Altered Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Prophase Progression Is Slightly Accelerated in the Absence of p53 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: CO Formation and Location Are Altered in p53 Absence Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Mutant Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Histology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Spermatocyte Spreads and Immunofluorescence Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: RNA Extraction and RT-qPCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Info: Title: p53 Controls Meiotic Prophase Progression and Crossover Formation Author: Marina Marcet-Ortega, Andros Maldonado-Linares, Maria López-Panadés and Ignasi Roig Subject: Meiosis initiates with the formation of double strand breaks (DSBs) throughout the genome. To avoid genomic instability, these DSBs need to be correctly repaired by homologous recombination. Surveillance mechanisms involving the DNA damage response (DDR) pathway ATM-CHK2-p53 can detect the persistence of unrepaired DBSs and activate the recombination-dependent arrest at the pachytene stage. However, a complete understanding of p53 functions under normal physiological conditions remains lacking. Here, we report a detailed analysis of the p53 role during meiotic prophase in mice spermatocytes. We show that the absence of p53 regulates prophase progression by slowing down the pachytene stage when the recombination-dependent arrest occurs. Furthermore, our results show that p53 is necessary for proper crossover (CO) formation and localization. Our study contributes to a deeper understanding of p53 roles during the meiotic prophase. 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