A Genetic Analysis of the Drosophila<i>mcm5</i>Gene Defines a Domain Specifically Required for Meiotic Recombination

Lake, Cathleen M.; Teeter, Kathy; Page, Scott L.; Nielsen, Rachel J.; Hawley, R. Scott

doi:10.1534/genetics.107.073551

Cited by 29 publications

(43 citation statements)

References 66 publications

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“…One clue as to how precondition gene products perform this function comes from their homology to the eukaryotic MCM family of proteins (MCM2-7), which form a heterohexameric helicase required for replication (Forsburg 2004;Blanton et al 2005;Lake et al 2007). Previous studies have also shown that the majority of MEI-218 protein was in the cytoplasm (Manheim et al 2002).…”

Section: Blocks To Nhej: the Precondition Gene Mei-218mentioning

confidence: 99%

Multiple Barriers to Nonhomologous DNA End Joining During Meiosis inDrosophila

Joyce¹,

Paul

Chen

et al. 2012

Genetics

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Repair of meiotic double-strand breaks (DSBs) uses the homolog and recombination to yield crossovers while alternative pathways such as nonhomologous end joining (NHEJ) are suppressed. Our results indicate that NHEJ is blocked at two steps of DSB repair during meiotic prophase: first by the activity of the MCM-like protein MEI-218, which is required for crossover formation, and, second, by Rad51-related proteins SPN-B (XRCC3) and SPN-D (RAD51C), which physically interact and promote homologous recombination (HR). We further show that the MCM-like proteins also promote the activity of the DSB repair checkpoint pathway, indicating an early requirement for these proteins in DSB processing. We propose that when a meiotic DSB is formed in the absence of both MEI-218 and SPN-B or SPN-D, a DSB substrate is generated that can enter the NHEJ repair pathway. Indeed, due to its high error rate, multiple barriers may have evolved to prevent NHEJ activity during meiosis.

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Section: Blocks To Nhej: the Precondition Gene Mei-218mentioning

confidence: 99%

Multiple Barriers to Nonhomologous DNA End Joining During Meiosis inDrosophila

Joyce¹,

Paul

Chen

et al. 2012

Genetics

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“…MCM 4 and MCM 5 have been proposed to be dispensable for endoreplication (35,36) on the basis of the observations that larval endoreplicating tissues are normal in mcm4 homozygotes and that endoreplication is completed in mcm5 SGs. In contrast, mcm6 larval size is reduced by 50%, indicating severe endoreplication defects (37).…”

Section: Orc1 Is Essential For Proliferationmentioning

confidence: 99%

The origin recognition complex is dispensable for endoreplication in Drosophila

Park

Asano

2008

Proc. Natl. Acad. Sci. U.S.A.

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The origin recognition complex (ORC) is an essential component of the prereplication complex (pre-RC) in mitotic cell cycles. The role of ORC as a foundation to assemble the pre-RC is conserved from yeast to human. Furthermore, in metazoans ORC plays a key role in determining the timing of replication initiation and origin usage. In this report we have produced and analyzed a Drosophila orc1 allele to investigate the roles of ORC1 in three different modes of DNA replication during development. As expected, ORC1 is essential for mitotic replication and proliferation in brains and imaginal discs, as well as for gene amplification in ovarian follicle cells. Surprisingly, however, ORC1 is not required for endoreplication. Decreased cell number in orc1 mutant salivary glands is consistent with the idea that undetectable levels of maternal ORC1 during embryogenesis fail to support further proliferation. Nevertheless, these cells begin endoreplicating normally and reach a final ploidy of >1000C in the absence of zygotic synthesis of ORC1. The dispensability of ORC is further supported by an examination of other ORC members, whereas Double-parked protein/Cdt1 and minichromosome maintenance proteins are apparently essential for endoreplication, implying that some aspects of initiation are shared among the three modes of DNA replication. This study provides insight into the physiologic roles of ORC during metazoan development and proposes that DNA replication initiation is governed differently in mitotic and endocycles.

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“…Some of these mutant alleles have been sequence verified by users and have been described in published studies (Lake et al 2007), suggesting that balanced lines are sufficiently stable to be useful for reverse genetics. In this report, we analyze the full set of mutations discovered in the Z-lines by Fly-TILL, and we evaluate the longterm stability of these lines.…”

mentioning

confidence: 96%

Retention of Induced Mutations in a Drosophila Reverse-Genetic Resource

et al. 2008

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Targeting induced local lesions in genomes (TILLING) is a reverse-genetic method for identifying point mutations in chemically mutagenized populations. For functional genomics, it is ideal to have a stable collection of heavily mutagenized lines that can be screened over an extended period of time. However, longterm storage is impractical for Drosophila, so mutant strains must be maintained by continual propagation of live cultures. Here we evaluate a strategy in which ethylmethane sulfonate (EMS) mutagenized chromosomes were maintained as heterozygotes with balancer chromosomes for .100 generations before screening. The strategy yielded a spectrum of point mutations similar to those found in previous studies of EMS-induced mutations, as well as 2.4% indels (insertions and deletions). Our analysis of 1887 point mutations in 148 targets showed evidence for selection against deleterious lesions and differential retention of lesions among targets on the basis of their position relative to balancer breakpoints, leading to a broad distribution of mutational densities. Despite selection and differential retention, the success of a userfunded service based on screening a large collection several years after mutagenesis indicates sufficient stability for use as a long-term reverse-genetic resource. Our study has implications for the use of balancer chromosomes to maintain mutant lines and provides the first large-scale quantitative assessment of the limitations of using breeding populations for repositories of genetic variability.

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A Genetic Analysis of the Drosophilamcm5Gene Defines a Domain Specifically Required for Meiotic Recombination

Cited by 29 publications

References 66 publications

Multiple Barriers to Nonhomologous DNA End Joining During Meiosis inDrosophila

Multiple Barriers to Nonhomologous DNA End Joining During Meiosis inDrosophila

The origin recognition complex is dispensable for endoreplication in Drosophila

Retention of Induced Mutations in a Drosophila Reverse-Genetic Resource

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