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Spontaneous and double-strand break repair-associated quasipalindrome and frameshift mutagenesis in budding yeast: role of mismatch repair.
Genetics
July 2024
Department of Biology and Rosenstiel Basic Medical Sciences Research Center MS029, Brandeis University, Waltham, MA 02454-9110, USA.
Although gene conversion (GC) in Saccharomyces cerevisiae is the most error-free way to repair double-strand breaks (DSBs), the mutation rate during homologous recombination is 1,000 times greater than during replication. Many mutations involve dissociating a partially copied strand from its repair template and re-aligning with the same or another template, leading to -1 frameshifts in homonucleotide runs, quasipalindrome (QP)-associated mutations and microhomology-mediated interchromosomal template switches. We studied GC induced by HO endonuclease cleavage at MATα, repaired by an HMR::KI-URA3 donor.
View Article and Find Full Text PDFCST-polymerase α-primase solves a second telomere end-replication problem.
Nature
March 2024
Laboratory for Cell Biology and Genetics, Rockefeller University, New York, NY, USA.
Telomerase adds G-rich telomeric repeats to the 3' ends of telomeres, counteracting telomere shortening caused by loss of telomeric 3' overhangs during leading-strand DNA synthesis ('the end-replication problem'). Here we report a second end-replication problem that originates from the incomplete duplication of the C-rich telomeric repeat strand (C-strand) by lagging-strand DNA synthesis. This problem is resolved by fill-in synthesis mediated by polymerase α-primase bound to Ctc1-Stn1-Ten1 (CST-Polα-primase).
View Article and Find Full Text PDFRPA interacts with Rad52 to promote meiotic crossover and noncrossover recombination.
Nucleic Acids Res
April 2024
Department of Life Sciences, Chung-Ang University, Seoul 06974, South Korea.
Article Synopsis
- Meiotic recombination starts with programmed double-strand breaks (DSBs) that create 3' single-stranded DNA (ssDNA) tails, where one end pairs with a homologous chromatid for DNA synthesis while the other remains attached to its sister.
- The process involves the capture and annealing of the second DSB end with the first end, facilitated by the protein Rad52, which works alongside the ssDNA binding protein, replication protein A (RPA).
- A failure in the Rad52-RPA interaction leads to an accumulation of RPA at crossover sites during meiotic prophase, suggesting that disrupted engagement during recombination might result in DSBs that resemble those seen in mitotic repair processes.
During prophase of meiosis I, programmed double strand breaks (DSBs) are processed into crossovers, a critical requirement for segregation of homologous chromosomes (homologs) and genome haploidization in sexually reproducing organisms. Crossovers form via homologous recombination in close temporospatial association with morphogenesis of the synaptonemal complex (SC), a proteinaceous structure that connects paired homologs along their length during the pachytene stage. Synapsis and recombination are a paradigm for the interplay between higher order chromosome structure and DNA metabolism, yet their temporal and functional relationship remains poorly understood.
View Article and Find Full Text PDFCST-Polymeraseα-primase solves a second telomere end-replication problem.
bioRxiv
January 2024
Laboratory for Cell Biology and Genetics, Rockefeller University, New York, USA.
Telomerase adds G-rich telomeric repeats to the 3' ends of telomeres, counteracting telomere shortening caused by loss of telomeric 3' overhangs during leading-strand DNA synthesis ("the end-replication problem"). We report a second end-replication problem that originates from the incomplete duplication of the C-rich telomeric repeat strand by lagging-strand synthesis. This problem is solved by CST-Polymeraseα(Polα)-primase fill-in synthesis.
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