Telomere maintenance and DNA repair are important processes that protect the genome. The essential helicase mRtel1 functions in homologous recombination repair and replication. In addition, telomeres in mRtel-deficient ES cells appear relatively stable in length, suggesting that mRtel1 is required to allow extension by telomerase.

CLIP-170 is a microtubule "plus-end-tracking protein" implicated in the control of microtubule dynamics, dynactin localization, and the linking of endosomes to microtubules. To investigate the function of mouse CLIP-170, we generated CLIP-170 knockout and GFP-CLIP-170 knock-in alleles. Residual CLIP-170 is detected in lungs and embryos of homozygous CLIP-170 knockout mice, but not in other tissues and cell types, indicating that we have generated a hypomorphic mutant. Homozygous CLIP-170 knockout mice are viable and appear normal. However, male knockout mice are subfertile and produce sperm with abnormal heads. Using the knock-in mice, we followed GFP-CLIP-170 expression and behavior in dissected, live testis tubules. We detect plus-end-tracking GFP-CLIP-170 in spermatogonia. As spermatogenesis proceeds, GFP-CLIP-170 expression increases and the fusion protein strongly marks syncytia of differentiated spermatogonia and early prophase spermatocytes. Subsequently GFP-CLIP-170 levels drop, but during spermiogenesis (post-meiotic development), GFP-CLIP-170 accumulates again and is present on spermatid manchettes and centrosomes. Bleaching studies show that, as spermatogenesis progresses, GFP-CLIP-170 converts from a mobile plus-end-tracking protein to a relatively immobile protein. We propose that CLIP-170 has a structural function in the male germline, in particular in spermatid differentiation and sperm head shaping.[Keywords: Microtubules; plus-end-tracking proteins; CLIP-170; spermatogenesis; spermatid manchette] Supplemental material is available at http://www.genesdev.org.

Telomere maintenance and DNA repair are crucial processes that protect the genome against instability. RTEL1, an essential iron–sulfur cluster-containing helicase, is a dominant factor that controls telomere length in mice and is required for telomere integrity. In addition, RTEL1 promotes synthesis-dependent strand annealing to direct DNA double-strand breaks into non-crossover outcomes during mitotic repair and in meiosis. Here, we review the role of RTEL1 in telomere maintenance and homologous recombination and discuss models linking RTEL1’s enzymatic activity to its function in telomere maintenance and DNA repair.

SummaryUbiquitin ligase Rad18 Sc localizes to the XY body and to other chromosomal regions that are unpaired and transcriptionally silenced during male meiotic prophase

Background: MMS19 was recently identified as part of the cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery. Results: MMS19 and MIP18 both interact with CIA and Fe-S proteins, and ANT2 binds to this complex. Conclusion: MMS19, MIP18, and ANT2 facilitate Fe-S cluster insertion into cytosolic Fe-S proteins. Significance: Identification of proteins in the CIA complex elucidates aspects of cytoplasmic iron-sulfur cluster assembly.

This study provides novel insight into the formation and resolution of telomere associations, which have been observed during key cellular processes such as mitosis, meiosis, and carcinogenesis. TRF1, a core component of the telomere protein complex, is a mediator of telomere associations in mammalian cells.

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