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Cancer etiology. Variation in cancer risk among tissues can be explained by the number of ste...

Tomasetti C1, Vogelstein B2.

Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that ... More

Speaker: Bennie
Date: 14.01.2015

Pharmacological targeting the ATR-CHK1-WEE1 axis involves balancing cell growth stimulation a...

Mak JP, Man WY, Ma HT, Poon RY.

The ATR-CHK1-WEE1 kinase cascade's functions in the DNA damage checkpoints are well established. Moreover, its roles in the unperturbed cell cycle are also increasingly being recognized. In this connection, a number of small-molecule inhibitors of ATR, CHK1, and WEE1 are being evaluated in clinical trials. Understanding precisely how cells respond to different concentratio... More

Speaker: Karen Akopyan
Date: 03.12.2014

HERC2/USP20 coordinates CHK1 activation by modulating CLASPIN stability

Min Zhu, Hongchang Zhao, Ji Liao and Xingzhi Xu

CLASPIN is an essential mediator in the DNA replication checkpoint, responsible for ATR (ataxia telangiectasia and Rad3-related protein)-dependent activation of CHK1 (checkpoint kinase 1). Here we found a dynamic signaling pathway that regulates CLASPIN turn over. Under unperturbed conditions, the E3 ubiquitin ligase HERC2 regulates the stability of the deubiquitinating en... More

Speaker: Erik
Date: 05.11.2014

Cyclin B-Cdk1 inhibits protein phosphatase PP2A-B55 via a Greatwall kinase-independent mechan...

Okumura E, Morita A, Wakai M, Mochida S, Hara M, Kishimoto T.

Entry into M phase is governed by cyclin B-Cdk1, which undergoes both an initial activation and subsequent autoregulatory activation. A key part of the autoregulatory activation is the cyclin B-Cdk1-dependent inhibition of the protein phosphatase 2A (PP2A)-B55, which antagonizes cyclin B-Cdk1. Greatwall kinase (Gwl) is believed to be essential for the autoregulatory activa... More

Speaker: Karen Akopyan
Date: 30.04.2014

ATM specifically mediates repair of double-strand breaks with blocked DNA ends

Alejandro Alvarez-Quilon, Almudena Serrano-Benitez, Jenna Ariel Lieberman, Cristina Quintero, Daniel...

Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signalling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still re... More

Speaker: Erik
Date: 26.03.2014

NFBD1/MDC1 Is Phosphorylated by PLK1 and Controls G2/M Transition through the Regulation of a...

Ando K, Ozaki T, Hirota T, Nakagawara A

Although it has been established that nuclear factor with BRCT domain 1/ mediator of the DNA damage checkpoint protein 1 (NFBD1/MDC1) is closely involved in DNA damage response, its possible contribution to the regulation of cell- cycle progression is unclear. In the present study, we have found for the first time that NFBD1 is phosphorylated by polo-like kinase 1 (PLK1) a... More

Speaker: Karen Akopyan
Date: 19.02.2014

Modulation of ATR-mediated DNA damage checkpoint response by cryptochrome 1

Kang TH, Leem SH.

Mammalian cryptochromes (Crys) are essential circadian clock factors implicated in diverse clock-independent physiological functions, including DNA damage responses. Here we show that Cry1 modulates the ATR-mediated DNA damage checkpoint (DDC) response by interacting with Timeless (Tim) in a time-of-day-dependent manner. The DDC capacity in response to UV irradiation showe... More

Speaker: Himjyot Jaiswal
Date: 12.02.2014

Phosphorylation of p53 by TAF1 Inactivates p53-Dependent Transcription in the DNA Damage Resp...

Wu Y, Lin JC, Piluso LG, Dhahbi JM, Bobadilla S, Spindler SR, Liu X.

While p53 activation has long been studied, the mechanisms by which its targets genes are restored to their preactivation state are less clear. We report here that TAF1 phosphorylates p53 at Thr55, leading to dissociation of p53 from the p21 promoter and inactivation of transcription late in the DNA damage response. We further show that cellular ATP level might act as a mo... More

Speaker: Arne
Date: 15.01.2014

ATR controls the UV-related upregulation of the CDKN1A mRNA in a Cdk1/HuR-dependent manner

Huda H. Al-Khalaf, Abdelilah Aboussekhra

Ultraviolet (UV) light is a carcinogenic agent that upregulates the expression of several genes involved in various cellular processes, including cell cycle checkpoints and apoptosis. The universal cyclin-dependent kinase inhibitor p21WAF1/Cip1 plays major roles in these processes, and the level of its corresponding message increases several times in response to UV-induced... More

Speaker: Karen Akopyan
Date: 04.12.2013

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Total articles: 41
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