scholarly journals Regulation of Minichromosome Maintenance (MCM) Helicase in Response to Replication Stress

10.5772/19284 ◽  
2011 ◽  
Author(s):  
Faria Zafar ◽  
Takuro Nakagaw
Keyword(s):  
Replication Stress ◽  
Minichromosome Maintenance ◽  
Mcm Helicase

scholarly journals DNA Binding by the Methanothermobacter thermautotrophicus Cdc6 Protein Is Inhibited by the Minichromosome Maintenance Helicase

2006 ◽  
Vol 188 (12) ◽  
pp. 4577-4580 ◽  
Author(s):  
Rajesh Kasiviswanathan ◽  
Jae-Ho Shin ◽  
Zvi Kelman
Keyword(s):  
Dna Binding ◽  
Binding Activity ◽  
Minichromosome Maintenance ◽  
Single Stranded Dna ◽  
Mutant Proteins ◽  
Dna Binding Activity ◽  
Double Stranded Dna ◽  
Mcm Helicase ◽  
Methanothermobacter Thermautotrophicus

ABSTRACT The Cdc6 proteins from the archaeon Methanothermobacter thermautotrophicus were previously shown to bind double-stranded DNA. It is shown here that the proteins also bind single-stranded DNA. Using minichromosome maintenance (MCM) helicase mutant proteins unable to bind DNA, it was found that the interaction of MCM with Cdc6 inhibits the DNA binding activity of Cdc6.

scholarly journals Polymorphism and Double Hexamer Structure in the Archaeal Minichromosome Maintenance (MCM) Helicase fromMethanobacterium thermoautotrophicum

2005 ◽  
Vol 280 (49) ◽  
pp. 40909-40915 ◽  
Author(s):  
Yacob Gómez-Llorente ◽  
Ryan J. Fletcher ◽  
Xiaojiang S. Chen ◽  
José M. Carazo ◽  
Carmen San Martín
Keyword(s):  
Minichromosome Maintenance ◽  
Mcm Helicase

scholarly journals The interplay of DNA binding, ATP hydrolysis and helicase activities of the archaeal MCM helicase

2011 ◽  
Vol 436 (2) ◽  
pp. 409-414 ◽  
Author(s):  
Li Phing Liew ◽  
Stephen D. Bell
Keyword(s):  
Dna Binding ◽  
Active Site ◽  
Atp Hydrolysis ◽  
Sulfolobus Solfataricus ◽  
Active Form ◽  
Dna Helicase ◽  
Atpase Domain ◽  
Minichromosome Maintenance ◽  
Conserved Residues ◽  
Mcm Helicase

The MCM (minichromosome maintenance) proteins of archaea are widely believed to be the replicative DNA helicase of these organisms. Most archaea possess a single MCM orthologue that forms homo-multimeric assemblies with a single hexamer believed to be the active form. In the present study we characterize the roles of highly conserved residues in the ATPase domain of the MCM of the hyperthermophilic archaeon Sulfolobus solfataricus. Our results identify a potential conduit for communicating DNA-binding information to the ATPase active site.

The MCM complex: (just) a replicative helicase?

2008 ◽  
Vol 36 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Alessandro Costa ◽  
Silvia Onesti
Keyword(s):  
Minichromosome Maintenance ◽  
Replicative Helicase ◽  
Aaa Atpase ◽  
Mcm Helicase ◽  
Eukaryotic Dna ◽  
Mcm Complex ◽  
Elongation Step ◽  
Hexameric Helicases

The MCM2–MCM7 (minichromosome maintenance 2–7) complex is involved both in the initiation and the elongation step of eukaryotic DNA replication and is believed to be the replicative helicase. Whereas the mechanism of DNA unwinding at the replication fork has been extensively investigated, the role of the MCM2–MCM7 complex during initiation has not yet been characterized by biochemical studies. Here we summarize the in vivo evidence which supports a role for the MCM complex in origin melting. In addition, we present an overview of the mechanism of action of a number of AAA+ (ATPase associated with various cellular activities) initiators and hexameric helicases, which can be used in turn as models for the steps of recognition, duplex melting, loading and nucleic acid translocation of the MCM helicase.

scholarly journals Mutations in Subdomain B of the Minichromosome Maintenance (MCM) Helicase Affect DNA Binding and Modulate Conformational Transitions

2008 ◽  
Vol 284 (9) ◽  
pp. 5654-5661 ◽  
Author(s):  
Elizabeth R. Jenkinson ◽  
Alessandro Costa ◽  
Andrew P. Leech ◽  
Ardan Patwardhan ◽  
Silvia Onesti ◽  
...  
Keyword(s):  
Dna Binding ◽  
Conformational Transitions ◽  
Minichromosome Maintenance ◽  
Mcm Helicase

Structure and function of the GINS complex, a key component of the eukaryotic replisome

2010 ◽  
Vol 425 (3) ◽  
pp. 489-500 ◽  
Author(s):  
Stuart A. MacNeill
Keyword(s):  
Replication Fork ◽  
Biochemical Analysis ◽  
Current Knowledge ◽  
Chromosomal Dna ◽  
Minichromosome Maintenance ◽  
Replication Process ◽  
Replicative Helicase ◽  
Cellular Life ◽  
Mcm Helicase ◽  
And Function

High-fidelity chromosomal DNA replication is fundamental to all forms of cellular life and requires the complex interplay of a wide variety of essential and non-essential protein factors in a spatially and temporally co-ordinated manner. In eukaryotes, the GINS complex (from the Japanese go-ichi-ni-san meaning 5-1-2-3, after the four related subunits of the complex Sld5, Psf1, Psf2 and Psf3) was recently identified as a novel factor essential for both the initiation and elongation stages of the replication process. Biochemical analysis has placed GINS at the heart of the eukaryotic replication apparatus as a component of the CMG [Cdc45–MCM (minichromosome maintenance) helicase–GINS] complex that most likely serves as the replicative helicase, unwinding duplex DNA ahead of the moving replication fork. GINS homologues are found in the archaea and have been shown to interact directly with the MCM helicase and with primase, suggesting a central role for the complex in archaeal chromosome replication also. The present review summarizes current knowledge of the structure, function and evolution of the GINS complex in eukaryotes and archaea, discusses possible functions of the GINS complex and highlights recent results that point to possible regulation of GINS function in response to DNA damage.

scholarly journals Intrinsic checkpoint deficiency during cell cycle re-entry from quiescence

2019 ◽  
Vol 218 (7) ◽  
pp. 2169-2184 ◽  
Author(s):  
Jacob Peter Matson ◽  
Amy M. House ◽  
Gavin D. Grant ◽  
Huaitong Wu ◽  
Joanna Perez ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Live Cell Imaging ◽  
Genome Instability ◽  
Replication Stress ◽  
S Phase ◽  
Minichromosome Maintenance ◽  
Cell Cycle Entry ◽  
Origin Licensing ◽  
Dna Replication Origins ◽  
Phase Entry

To maintain tissue homeostasis, cells transition between cell cycle quiescence and proliferation. An essential G1 process is minichromosome maintenance complex (MCM) loading at DNA replication origins to prepare for S phase, known as origin licensing. A p53-dependent origin licensing checkpoint normally ensures sufficient MCM loading before S phase entry. We used quantitative flow cytometry and live cell imaging to compare MCM loading during the long first G1 upon cell cycle entry and the shorter G1 phases in the second and subsequent cycles. We discovered that despite the longer G1 phase, the first G1 after cell cycle re-entry is significantly underlicensed. Consequently, the first S phase cells are hypersensitive to replication stress. This underlicensing results from a combination of slow MCM loading with a severely compromised origin licensing checkpoint. The hypersensitivity to replication stress increases over repeated rounds of quiescence. Thus, underlicensing after cell cycle re-entry from quiescence distinguishes a higher-risk first cell cycle that likely promotes genome instability.

scholarly journals Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast

2015 ◽  
Vol 26 (19) ◽  
pp. 3439-3450 ◽  
Author(s):  
Sarah A. Sabatinos ◽  
Nimna S. Ranatunga ◽  
Ji-Ping Yuan ◽  
Marc D. Green ◽  
Susan L. Forsburg
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Chromosome Rearrangement ◽  
Chromosome Instability ◽  
Replication Stress ◽  
Parent Nucleus ◽  
S Phase ◽  
Yeast Mutant ◽  
Mcm Helicase ◽  
Dna Replication Stress

DNA replication stress causes genome mutations, rearrangements, and chromosome missegregation, which are implicated in cancer. We analyze a fission yeast mutant that is unable to complete S phase due to a defective subunit of the MCM helicase. Despite underreplicated and damaged DNA, these cells evade the G2 damage checkpoint to form ultrafine bridges, fragmented centromeres, and uneven chromosome segregations that resembles micronuclei. These micronuclei retain DNA damage markers and frequently rejoin with the parent nucleus. Surviving cells show an increased rate of mutation and chromosome rearrangement. This first report of micronucleus-like segregation in a yeast replication mutant establishes underreplication as an important factor contributing to checkpoint escape, abnormal chromosome segregation, and chromosome instability.

scholarly journals The Methanothermobacter thermautotrophicus Cdc6-2 Protein, the Putative Helicase Loader, Dissociates the Minichromosome Maintenance Helicase

2008 ◽  
Vol 190 (11) ◽  
pp. 4091-4094 ◽  
Author(s):  
Jae-Ho Shin ◽  
Gun Young Heo ◽  
Zvi Kelman
Keyword(s):  
Minichromosome Maintenance ◽  
Mcm Helicase ◽  
Protein Functions ◽  
Mcm Complex ◽  
Methanothermobacter Thermautotrophicus

ABSTRACT The Cdc6-1 and -2 proteins from the archaeon Methanothermobacter thermautotrophicus were previously shown to bind the minichromosome maintenance (MCM) helicase. It is shown here that Cdc6-2 protein dissociates the MCM complex. This observation supports the hypothesis that the Cdc6-2 protein functions as a helicase loader.

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