A mechanical basis for chromosome function

Kleckner, Nancy; Zickler, Denise; Jones, Gareth R.; Dekker, Job; Padmore, Ruth; Henle, Jim; Hutchinson, John N.

doi:10.1073/pnas.0402724101

Cited by 290 publications

(402 citation statements)

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“…LinEs and crossing over: It has been proposed that axial proteins, such as Red1 in S. cerevisiae, function to introduce a compaction stress into the chromosomal structure that facilitates crossing over and might play a role in genetic interference (Blat et al 2002;Kleckner et al 2004), the latter not being apparent in S. pombe (Munz 1994). Our data are not inconsistent with LinEs generating a recombinogenic compaction stress that may enhance crossing over to above the level observed in the rec10-155 mutant.…”

Section: Discussionmentioning

confidence: 99%

“…The LinE structures of S. pombe and the AEs of Saccharomyces cerevisiae have conserved common features and the key structural components in the two organisms, Rec10 (S. pombe) and Red1 (S. cerevisiae), exhibit some amino acid conservation (Lorenz et al 2004). This structural conservation and the absence of a visible SC in S. pombe strongly suggest that AEs serve some function other than providing a precursory platform for SC formation; they may function by contributing to the establishment of chromosomal mechanical forces of compaction, which have been proposed to regulate meiotic recombination (Blat et al 2002;Kleckner et al 2004). Furthermore, AEs (and possibly LinEs) appear to play a critical role in directing interhomolog recombination, precluding intersister recombination events (Schwacha and Kleckner 1997;Thompson and Stahl 1999), possibly by providing a platform for Hop1 protein-mediated dimerization of the Mek1 kinase, which, like Red1 and Hop1, is required to promote interhomolog recombination (Niu et al 2005).…”

Section: S Exual Reproduction In Most Eukaryotes Involvesmentioning

confidence: 99%

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Linear Element-Independent Meiotic Recombination in Schizosaccharomyces pombe

et al. 2006

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Most organisms form protein-rich, linear, ladder-like structures associated with chromosomes during early meiosis, the synaptonemal complex. In Schizosaccharomyces pombe, linear elements (LinEs) are thread-like, proteinacious chromosome-associated structures that form during early meiosis. LinEs are related to axial elements, the synaptonemal complex precursors of other organisms. Previous studies have led to the suggestion that axial structures are essential to mediate meiotic recombination. Rec10 protein is a major component of S. pombe LinEs and is required for their development. In this report we study recombination in a number of rec10 mutants, one of which (rec10-155) does not form LinEs, but is predicted to encode a truncated Rec10 protein. This mutant has levels of crossing over and gene conversion substantially higher than a rec10 null mutant (rec10-175) and forms cytologically detectable Rad51 foci indicative of meiotic recombination intermediates. These data demonstrate that while Rec10 is required for meiotic recombination, substantial meiotic recombination can occur in rec10 mutants that do not form LinEs, indicating that LinEs per se are not essential for all meiotic recombination.

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Section: Discussionmentioning

confidence: 99%

Section: S Exual Reproduction In Most Eukaryotes Involvesmentioning

confidence: 99%

Linear Element-Independent Meiotic Recombination in Schizosaccharomyces pombe

et al. 2006

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“…Measurement of chromosome mechanical properties is also important to understanding the mitotic apparatus, which is in part regulated via roughly nanonewton forces (1 nN=10 j9 newtons; a newton approximately is the gravitational force exerted by a 100 gram mass on the earth) generated in chromosomes during mitosis (Nicklas 1983, Skibbens et al 1995, Skibbens & Salmon 1997, Nicklas et al 2001, Gardner et al 2005. Chromosome mechanics has been suggested to play a variety of roles in mitotic and meiotic chromosome dynamics (Kleckner 1995, Marko & Siggia 1997, Kleckner et al 2004.…”

Section: Chromosome-stretching Experimentsmentioning

confidence: 99%

Micromechanical studies of mitotic chromosomes

2008

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Mitotic chromosomes respond elastically to forces in the nanonewton range, a property important to transduction of stresses used as mechanical regulatory signals during cell division. In addition to being important biologically, chromosome elasticity can be used as a tool for investigating the folding of chromatin. This paper reviews experiments studying stretching and bending stiffness of mitotic chromosomes, plus experiments where changes in chromosome elasticity resulting from chemical and enzyme treatments were used to analyse connectivity of chromatin inside chromosomes. Experiments with nucleases indicate that non-DNA elements constraining mitotic chromatin must be isolated from one another, leading to the conclusion that mitotic chromosomes have a chromatin Fnetwork_ or Fgel_ organization, with stretches of chromatin strung between Fcrosslinking_ points. The as-yet unresolved questions of the identities of the putative chromatin crosslinkers and their organization inside mitotic chromosomes are discussed.

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Section: Introductionmentioning

confidence: 99%

“…DNA tension is physiologically relevant because pulling of chromatin is likely to occur in vivo, given the large forces that can be produced by RNA polymerase (Yin et al, 1995;Wang et al, 1998), and DNA polymerase (Maier et al, 2000). Tension in chromatin has been suggested to play a role in regulation of various aspects of chromosome dynamics (Marko and Siggia, 1997a, b;Kleckner et al, 2004), via mechanisms including force-driven modification of chromatin structure.The concept underlying force-extension studies of chromatin assembly and disassembly is sketched roughly in Figure 1, applied to the example of the nucleosome core histone octamer. Force applied to the DNA favors nucleosome disassembly, because this liberates wrapped DNA of length l (expected to be ϳ150 base pairs ϭ 50 nm for a whole nucleosome), doing mechanical work equal to the product of force f and l (Marko and Siggia, 1997a).…”

mentioning

confidence: 99%

Micromanipulation Studies of Chromatin Fibers in Xenopus Egg Extracts Reveal ATP-dependent Chromatin Assembly Dynamics

Yan

Maresca

Skoko

et al. 2007

MBoC

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We have studied assembly of chromatin using Xenopus egg extracts and single DNA molecules held at constant tension by using magnetic tweezers. In the absence of ATP, interphase extracts were able to assemble chromatin against DNA tensions of up to 3.5 piconewtons (pN). We observed force-induced disassembly and opening-closing fluctuations, indicating our experiments were in mechanochemical equilibrium. Roughly 50-nm (150-base pair) lengthening events dominated force-driven disassembly, suggesting that the assembled fibers are chiefly composed of nucleosomes. The ATP-depleted reaction was able to do mechanical work of 27 kcal/mol per 50 nm step, which provides an estimate of the free energy difference between core histone octamers on and off DNA. Addition of ATP led to highly dynamic behavior with time courses exhibiting processive runs of assembly and disassembly not observed in the ATP-depleted case. With ATP present, application of forces of 2 pN led to nearly complete fiber disassembly. Our study suggests that ATP hydrolysis plays a major role in nucleosome rearrangement and removal and that chromatin in vivo may be subject to highly dynamic assembly and disassembly processes that are modulated by DNA tension. INTRODUCTIONTranscription, replication, and other in vivo DNA processing in eukaryotes take place in the context of chromatin. The processive nature of these activities, and the necessity to disrupt histone-DNA contacts to accomplish them, suggests that chromatin must be dynamic in its structure, with actively transcribing genes perhaps in a continual state of structural rearrangement. The simplest example of chromatin rearrangement that would allow base pair access is displacement or dissociation of part or all of the histone octamer (Felsenfeld, 1996).Chromosome visualization in vivo gives insight into chromatin dynamics at large length scales (Belmont, 2003;Levi et al., 2005) but is as yet unable to reveal events at the scale of individual nucleosome displacements. A complementary approach is to study individual chromatin fibers by using micromanipulation (Cui and Bustamante, 2000;Ladoux et al., 2000;Bennink et al., 2001;Brower-Toland et al., 2002;Leuba et al., 2003;Claudet et al., 2005;Gemmen et al., 2005;Bancaud et al., 2006). A major objective of such experiments has been the study of mechanically triggered changes in protein-DNA contacts, with an emphasis on force-driven opening of nucleosomes.However, biophysical micromanipulation experiments offer possibilities beyond simply disassembling chromatin by force; experiments in "active" solutions containing chromatin-organizing or chromatin-processing enzymes permit direct observation of chromatin dynamics, and they can reveal details of structure and mechanism concerning compaction of DNA into chromatin, chromatin remodeling, gene expression in chromatin, mitotic chromosome condensation, and how such processes are affected by DNA tension. DNA tension is physiologically relevant because pulling of chromatin is likely to occur in vivo, given the larg...

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A mechanical basis for chromosome function

Abstract: We propose that chromosome function is governed by internal mechanical forces generated by programmed tendencies for expansion of the DNA͞chromatin fiber against constraining features.

Cited by 290 publications

References 36 publications

Linear Element-Independent Meiotic Recombination in Schizosaccharomyces pombe

Linear Element-Independent Meiotic Recombination in Schizosaccharomyces pombe

Micromechanical studies of mitotic chromosomes

Micromanipulation Studies of Chromatin Fibers in Xenopus Egg Extracts Reveal ATP-dependent Chromatin Assembly Dynamics

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