A common sequence motif associated with recombination hot spots and genome instability in humans

2008 ◽  
Vol 40 (9) ◽  
pp. 1124-1129 ◽  
Author(s):  
Simon Myers ◽  
Colin Freeman ◽  
Adam Auton ◽  
Peter Donnelly ◽  
Gil McVean
2007 ◽  
Vol 6 (11) ◽  
pp. 2072-2080 ◽  
Author(s):  
Kouji Hirota ◽  
Walter W. Steiner ◽  
Takehiko Shibata ◽  
Kunihiro Ohta

ABSTRACT The ade6-M26 meiotic recombination hot spot of fission yeast is defined by a cyclic AMP-responsive element (CRE)-like heptanucleotide sequence, 5′-ATGACGT-3′, which acts as a binding site for the Atf1/Pcr1 heterodimeric transcription factor required for hot spot activation. We previously demonstrated that the local chromatin around the M26 sequence motif alters to exhibit higher sensitivity to micrococcal nuclease before the initiation of meiotic recombination. In this study, we have examined whether or not such alterations in chromatin occur at natural meiotic DNA double-strand break (DSB) sites in Schizosaccharomyces pombe. At one of the most prominent DSB sites, mbs1 (meiotic break site 1), the chromatin structure has a constitutively accessible configuration at or near the DSB sites. The establishment of the open chromatin state and DSB formation are independent of the CRE-binding transcription factor, Atf1. Analysis of the chromatin configuration at CRE-dependent DSB sites revealed both differences from and similarities to mbs1. For example, the tdh1 + locus, which harbors a CRE consensus sequence near the DSB site, shows a meiotically induced open chromatin configuration, similar to ade6-M26. In contrast, the cds1 + locus is similar to mbs1 in that it exhibits a constitutive open configuration. Importantly, Atf1 is required for the open chromatin formation in both tdh1 + and cds1 +. These results suggest that CRE-dependent meiotic chromatin changes are intrinsic processes related to DSB formation in fission yeast meiosis. In addition, the results suggest that the chromatin configuration in natural meiotic recombination hot spots can be classified into at least three distinct categories: (i) an Atf1-CRE-independent constitutively open chromatin configuration, (ii) an Atf1-CRE-dependent meiotically induced open chromatin configuration, and (iii) an Atf1-CRE-dependent constitutively open chromatin configuration.


2005 ◽  
Vol 25 (20) ◽  
pp. 9054-9062 ◽  
Author(s):  
Walter W. Steiner ◽  
Gerald R. Smith

ABSTRACT The M26 hot spot of meiotic recombination in Schizosaccharomyces pombe is the eukaryotic hot spot most thoroughly investigated at the nucleotide level. The minimum sequence required for M26 activity was previously determined to be 5′-ATGACGT-3′. Originally identified by a mutant allele, ade6-M26, the M26 heptamer sequence occurs in the wild-type S. pombe genome approximately 300 times, but it has been unclear whether any of these are active hot spots. Recently, we showed that the M26 heptamer forms part of a larger consensus sequence, which is significantly more active than the heptamer alone. We used this expanded sequence as a guide to identify a smaller number of sites most likely to be active hot spots. Ten of the 15 sites tested showed meiotic DNA breaks, a hallmark of recombination hot spots, within 1 kb of the M26 sequence. Among those 10 sites, one occurred within a gene, cds1 +, and hot spot activity of this site was confirmed genetically. These results are, to our knowledge, the first demonstration in any organism of a simple, defined nucleotide sequence accurately predicting the locations of natural meiotic recombination hot spots. M26 may be the first example among a diverse group of simple sequences that determine the distribution, and hence predictability, of meiotic recombination hot spots in eukaryotic genomes.


Matter ◽  
2021 ◽  
Author(s):  
Qingzhi An ◽  
Fabian Paulus ◽  
David Becker-Koch ◽  
Changsoon Cho ◽  
Qing Sun ◽  
...  

1994 ◽  
Vol 7 (3) ◽  
pp. 420-424 ◽  
Author(s):  
Rene Hubert ◽  
Marcy MacDonald ◽  
James Gusella ◽  
Norman Arnheim

mBio ◽  
2017 ◽  
Vol 8 (6) ◽  
Author(s):  
Ke Zhang ◽  
Xue-Chang Wu ◽  
Dao-Qiong Zheng ◽  
Thomas D. Petes

ABSTRACT Although meiosis in warm-blooded organisms takes place in a narrow temperature range, meiosis in many organisms occurs over a wide variety of temperatures. We analyzed the properties of meiosis in the yeast Saccharomyces cerevisiae in cells sporulated at 14°C, 30°C, or 37°C. Using comparative-genomic-hybridization microarrays, we examined the distribution of Spo11-generated meiosis-specific double-stranded DNA breaks throughout the genome. Although there were between 300 and 400 regions of the genome with high levels of recombination (hot spots) observed at each temperature, only about 20% of these hot spots were found to have occurred independently of the temperature. In S. cerevisiae , regions near the telomeres and centromeres tend to have low levels of meiotic recombination. This tendency was observed in cells sporulated at 14°C and 30°C, but not at 37°C. Thus, the temperature of sporulation in yeast affects some global property of chromosome structure relevant to meiotic recombination. Using single-nucleotide polymorphism (SNP)-specific whole-genome microarrays, we also examined crossovers and their associated gene conversion events as well as gene conversion events that were unassociated with crossovers in all four spores of tetrads obtained by sporulation of diploids at 14°C, 30°C, or 37°C. Although tetrads from cells sporulated at 30°C had slightly (20%) more crossovers than those derived from cells sporulated at the other two temperatures, spore viability was good at all three temperatures. Thus, despite temperature-induced variation in the genetic maps, yeast cells produce viable haploid products at a wide variety of sporulation temperatures. IMPORTANCE In the yeast Saccharomyces cerevisiae , recombination is usually studied in cells that undergo meiosis at 25°C or 30°C. In a genome-wide analysis, we showed that the locations of genomic regions with high and low levels of meiotic recombination (hot spots and cold spots, respectively) differed dramatically in cells sporulated at 14°C, 30°C, and 37°C. Thus, in yeast, and likely in other non-warm-blooded organisms, genetic maps are strongly affected by the environment.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaohua Wang ◽  
Ping Xu ◽  
Yan Ren ◽  
Liang Yin ◽  
Shuangling Li ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document