Partial hydrolysis enhances the inhibitory effects of konjac glucomannan from Amorphophallus konjac C. Koch on DNA damage induced by fecal water in Caco-2 cells

Most Cyclin-dependent kinases (Cdks) are redundant for normal cell division. Here we tested whether these redundancies are maintained during cell cycle recovery after a DNA damage-induced arrest in G1. Using non-transformed RPE-1 cells, we find that while Cdk4 and Cdk6 act redundantly during normal S-phase entry, they both become essential for S-phase entry after DNA damage in G1. We show that this is due to a greater overall dependency for Cdk4/6 activity, rather than to independent functions of either kinase. In addition, we show that inactivation of pocket proteins is sufficient to overcome the inhibitory effects of complete Cdk4/6 inhibition in otherwise unperturbed cells, but that this cannot revert the effects of Cdk4/6 inhibition in DNA damaged cultures. Indeed, we could confirm that, in addition to inactivation of pocket proteins, Cdh1-dependent anaphase-promoting complex/cyclosome (APC/CCdh1) activity needs to be inhibited to promote S-phase entry in damaged cultures. Collectively, our data indicate that DNA damage in G1 creates a unique situation where high levels of Cdk4/6 activity are required to inactivate pocket proteins and APC/CCdh1 to promote the transition from G1 to S phase.

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Comparative Effects of Cellulose and Soluble Fibers (Pectin, Konjac Glucomannan, Inulin) on Fecal Water Toxicity toward Caco-2 Cells, Fecal Bacteria Enzymes, Bile Acid, and Short-Chain Fatty Acids

Journal of Agricultural and Food Chemistry ◽

10.1021/jf102127k ◽

2010 ◽

Vol 58 (18) ◽

pp. 10277-10281 ◽

Cited By ~ 20

Author(s):

Hsiao-Ling Chen ◽

You-Mei Lin ◽

Yi-Chun Wang

Keyword(s):

Fatty Acids ◽

Bile Acid ◽

Short Chain Fatty Acids ◽

Konjac Glucomannan ◽

Short Chain ◽

Fecal Bacteria ◽

Water Toxicity ◽

Fecal Water ◽

Chain Fatty Acids

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Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1816539115 ◽

2018 ◽

Vol 115 (51) ◽

pp. E11961-E11969 ◽

Cited By ~ 14

Author(s):

Tai-Yuan Yu ◽

Michael T. Kimble ◽

Lorraine S. Symington

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Double Strand Breaks ◽

Dna Double Strand Breaks ◽

Inhibitory Effects ◽

Checkpoint Signaling ◽

Synthetic Lethal ◽

Strand Breaks ◽

Damage Response ◽

End Resection

The Mre11-Rad50-Xrs2NBS1 complex plays important roles in the DNA damage response by activating the Tel1ATM kinase and catalyzing 5′–3′ resection at DNA double-strand breaks (DSBs). To initiate resection, Mre11 endonuclease nicks the 5′ strands at DSB ends in a reaction stimulated by Sae2CtIP. Accordingly, Mre11-nuclease deficient (mre11-nd) and sae2Δ mutants are expected to exhibit similar phenotypes; however, we found several notable differences. First, sae2Δ cells exhibit greater sensitivity to genotoxins than mre11-nd cells. Second, sae2Δ is synthetic lethal with sgs1Δ, whereas the mre11-nd sgs1Δ mutant is viable. Third, Sae2 attenuates the Tel1-Rad53CHK2 checkpoint and antagonizes Rad953BP1 accumulation at DSBs independent of Mre11 nuclease. We show that Sae2 competes with other Tel1 substrates, thus reducing Rad9 binding to chromatin and to Rad53. We suggest that persistent Sae2 binding at DSBs in the mre11-nd mutant counteracts the inhibitory effects of Rad9 and Rad53 on Exo1 and Dna2-Sgs1–mediated resection, accounting for the different phenotypes conferred by mre11-nd and sae2Δ mutations. Collectively, these data show a resection initiation independent role for Sae2 at DSBs by modulating the DNA damage checkpoint.

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Tracing the Evolution and Economic Potential of Konjac Glucomannan in Amorphophallus species (Araceae) using Molecular Phylogeny and RAPD Markers

Phytotaxa ◽

10.11646/phytotaxa.282.2.1 ◽

2016 ◽

Vol 282 (2) ◽

pp. 81 ◽

Cited By ~ 1

Author(s):

ORACHORN MEKKERDCHOO ◽

CHALEEDA BOROMPICHAICHARTKUL ◽

ALLISON PERRIGO ◽

GEORGE SRZEDNICKI ◽

CHEUNJIT PRAKITCHAIWATTANA ◽

...

Keyword(s):

Rapd Markers ◽

Genetic Relationships ◽

Its Region ◽

Pharmaceutical Products ◽

Konjac Glucomannan ◽

Closely Related Species ◽

Dna Variation ◽

Amorphophallus Konjac ◽

Genome Wide ◽

Present Understanding

The genus Amorphophallus is an economically important taxon that is abundant in Old World tropical forests (Asia, Oceania and Africa). It includes many species that are used with increasing frequency as a source of food and pharmaceutical products worldwide. Amorphophallus konjac is an important economic crop and has been used widely in China and Japan for commercial konjac glucomannan (KGM) production. However, the species’ range does not extend to Thailand, where other closely related species may be more suitable for commercial KGM production. Present understanding of genetic relationships among Thai Amorphophallus species is still limited, and the connection between evolutionary history and KGM content is unknown. Here, the genetic relationships among various accessions of Amorphophallus spp. collected in Thailand are investigated using the chloroplast trnL-trnF spacer, nuclear ribosomal internal transcribed spacer (ITS) region and the second intron of LEAFY (FLint2) together with genome-wide DNA variation analysis, Randomly Amplified Polymorphic DNA (RAPD) technique. RAPD primers are also developed to quickly and efficiently identify species producing high levels of KGM. This study finds that two monophyletic clades include high KGM content species. RAPD analyses indicate that primer AC-10 generates specific bands identifying species belonging only to the high and medium KGM content clades. These primers can be used as a screening tool for economical species, aiming at improving the industrial production of KGM in Thailand and the world.

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