2013 July/August Beacon

Page 1

King Abdullah University of Science and Technology

BEACON ‫املنـارة‬ at Thuwal, Kingdom of Saudi Arabia

July/August 2013 / Ramadan/Shawwal 1434 Volume 3, Issue No. 11

the

www.kaust.edu.sa

‫ شامو‬-‫مرحبًا بالربوفسور جان لو‬ WELCOME PROFESSOR JEAN-LOU CHAMEAU

‫تولى الدكتور جان – لو شامو منصب رئيس جامعة الملك عبداهلل للعلوم والتقنية بتاريخ األول من شهر يوليو لعام‬ .‫ إلى أسرة جامعة الملك عبداهلل‬،‫ ويطيب لنا أن نرحب بانضمامه هو وزوجته الدكتورة كارول كارمايكل‬.2013 PROFESSOR Jean-Lou Chameau joined KAUST as the new president on July 1. We welcome him and his wife, Dr. Carol Carmichael, to the KAUST family.

‫قام علماء وباحثني من جامعة امللك عبداهلل بإجراء‬ ‫جتارب على نوع جديد وخاص من األغشية املسامية‬ ‫املتجانسة واليت ميكن أن تستخدم يف التطبيقات‬ ‫ وقاد هذا‬.‫الطبية احليوية أو معاجلة وحتلية املياه‬ ‫البحث االستاذ املشارك يف اهلندسة الكيميائية‬ ‫والبيولوجية وعضو يف مركز أحباث حتلية وإعادة‬ ،‫استخدام املياه يف اجلامعة الدكتور سوزانا نونيز‬ -‫وشاركها يف هذا البحث كل من الربوفسور كالوس‬ ‫فيكتور بينيمان أستاذ اهلندسة الكيميائية والبيولوجية‬ ‫يف مركز األغشية املتطورة واملواد املسامية يف‬ ‫ إضافة إىل طاليب الدكتوراه‬،‫جامعة امللك عبداهلل‬ .‫ديبورا سالومون ماركيز ونيكوال مورينو شابارو‬

Figure 1. Dynamics of FEN1 Bending of DF-6,1 by smFRET (A) A schematic diagram of FEN1 reaction on DF-6,1. (B) Structure of FEN1 in complex with SF-0,1; Protein Data Bank (PDB) code 3Q8L (Tsutakawa et al., 2011). The conserved and unique structural features that interact with the bent DNA conformation are depicted and labeled in the same color. ASSISTANT Professor of Chemistry and Biology and Principal Investigator of the Laboratory of DNA Replication and Recombination Dr. Samir M. Hamdan and his team have published a groundbreaking paper on the mechanism of flap endonuclease 1 (FEN1) in the journal Cell Reports. The other authors of the paper entitled "Sequential and Multistep Substrate Interrogation Provides the Scaffold for Specificity in Human Flap Endonuclease 1" are Mohamed A. Sobhy, Luay I.

Principal Investigator of the Laboratory of DNA Replication and Recombination Dr. Hamdan and his team have published a groundbreaking paper in the journal Cell Reports.

Joudeh, Xiaojuan Huang, and Masateru Takahashi. 5' nucleases, the superfamily to which FEN1 belongs, represent

mechanisms occurring during this process. The KAUST scientists were

structure-specific nucleases essential for DNA replication, repair, and

able to build a timeline of up to seven intermediary steps before FEN1

2 ‫تتمه صفحة‬

recombination. Deficiencies in their genes have been linked to sev-

commits to catalysis. Such information cannot be accessed through

eral types of cellular stress and genomic instability. Their outstanding

conventional approaches.

KAUST RESEARCHERS INVESTIGATE PROPERTIES OF BLOCK COPOLYMER MEMBRANES

puzzle is that they are highly conserved proteins, yet they recognize a

These findings will influence how researchers think about the mecha-

diverse range of RNA and DNA structures and cleave them primarily at

nism of other members of 5' nucleases and provide a new concept as to

the same position relative to a 5' end of a junction.

how biological macromolecules can diversify their substrate specificity

KAUST researchers examined a type of mem-

Structural studies propose a solution for this geometrical puzzle by

while maintaining a high degree of structural similarities.

capturing a DNA-bending intermediary step that positions the 5' end in

Dr. Hamdan explained that the surprising finding is that FEN1

the enzyme's active pocket and unifies the 5' nuclease's cleavage site.

utilizes a highly complex mechanism that sequentially verifies all

However, these structures remain a static image of the DNA-bending

substrate features before inducing the superfamily unifying DNA-

brane with uniformly sized pores that could be

intermediary step based on which speculation was made to address

bending intermediary. This sequential and multistep substrate

used in biomedical or water treatment appli-

the most important questions regarding how this intermediary step is

recognition process provides a scaffold that allows different 5' nucle-

cations in a paper published recently in the

induced and how 5' nucleases utilize the same intermediary step to rec-

ases to recognize different substrates and restrict the induction of

journal Soft Matter (http://pubs.rsc.org/en/

ognize a diverse range of substrates.

DNA bending to the last common step. "We hope that our findings will

Content/ArticleLanding/2013/SM/c3sm27475f).

The team from KAUST's Division of Biological and Environmental

“The membranes examined in the paper are

Sciences and Engineering employed a sophisticated single molecule

very specific,” says Dr. Suzana Nunes, Associate

imaging technique, Förster resonance energy transfer (smFRET), to cap-

MEMBRANES | Continued on p2

ture "molecular movies" detailing the structure, dynamics, and reaction

INSIDE:

Research 1-2

News 3

serve as a base to design inhibitors against FEN1, whose expression is highly correlated with tumor aggressiveness," said Prof. Hamdan. The article may be accessed at Cell Report. Volume 3, Issue 6, 17851794, 06 June 2013. 

Community 4

Reprinted from Cell Reports, 3, Mohamed A. Sobhy et al, Sequential and Multistep Substrate Interrogation Provides the Scaffold for Specificity in Human Flap Endonuclease 1, 1785-1794, 2013, with permission from Elsevier.

Image reproduced by permission of Suzana P Nunes and The Royal Society of Chemistry from Soft Matter, 2013, 9, 5557-5564, DOI: 10.1039/C3SM27475F. Prof. Suzana Nunes and colleagues’ work was featured on the inside front cover of the journal Soft Matter. Image by KAUST Scientific Illustrator Olga Kasimova.

‫باحثون من جامعة امللك عبداهلل‬ ‫يدرسون خصائص أغشية كتلة‬ ‫البوليمر املشرتك‬

CAPTURING MOLECULAR MOVIES OF DNA REPLICATION AND REPAIR


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