CH391L/S2013

Molecular Mechanisms of Genome Maintenance

CH 391L (Spring 2013)

Unique # 52955

Wednesdays 2–5 PM, WEL 3.422, Professor: Finkelstein

Instructor: Dr. Ilya Finkelstein

Office Hours: by appointment only

Office: MBB 3.422AA

Syllabus

Index of All CH391/S2013 Pages

View Recent Changes to CH391/S2013 Pages

Introduction

Topics: This course will focus on current developments in understanding the molecular mechanisms of genome maintenance and cancerogenesis. A strong emphasis of the course will be to understand the methods and techniques that have enabled modern breakthroughs in understanding genome stability. The course will rely heavily on primary literature and class presentations.

Prerequisite: Biochemistry (CH339K and CH339L) or equivalent. Undergraduate students must have the instructor's permission to register for this course.

Course web page: The course web site on the OpenWetWare (OWW) Wiki will be used to complete assignments. Participants will be required to register an account on OWW and learn to edit this Wiki.

Assignments

A Wiki Editing Tutorial borrowed from (The Other) CH391L

Due January 23, 2013

1. Alesha S: Spontaneous DNA breakage in single living Escherichia coli cells.
   1. First oral presentation
   2. Wiki article -- first draft
2. Tanya R: Activation of DSB Processing Requires Phosphorylation of CtIP by ATR.
   1. First oral presentation
   2. Wiki article -- first draft
      1. CH391L/S2013 Tanya Raymond Jan 23 2013
3. Hala Ouzon: Purified human BRCA2 stimulates RAD51-mediated recombination.
   1. First oral presentation
   2. Wiki article -- first draft
      1. CH391L/S2013 Hala Ouzon Jan 23 2013

Due January 30, 2013

1. Alesha S: Spontaneous DNA breakage in single living Escherichia coli cells.
   1. Second oral presentation
   2. Wiki article -- final draft

     *CH391L/S2013 Alesha Stewart Jan 30 2013

1. Tanya R: Activation of DSB Processing Requires Phosphorylation of CtIP by ATR.
   1. Second oral presentation
   2. Wiki article -- final draft
      1. CH391L/S2013 Tanya Raymond Jan 30 2013
2. Hala Ouzon: Purified human BRCA2 stimulates RAD51-mediated recombination.
   1. Second oral presentation
   2. Wiki article -- final draft
      1. CH391L/S2013 Hala Ouzon Jan 30 2013
3. Logan M: Activation of the cellular DNA damage Response in the Absence of DNA Lesions.
   1. First oral presentation
   2. Wiki article -- first draft
      1. CH391L/S2013 Logan R Myler Jan 30 2013

Due February 6, 2013

1. Tanya R: Recombination-restarted replication makes inverted chromosome fusions at inverted repeats
   1. First Oral Presentation
   2. Wiki article -- first draft
      1. CH391L/S2013 Tanya Raymond Feb 6 2013
2. Taylor Pursell: [1]
   1. First Oral Presentation
   2. Wiki Article First Draft: CH391L/S2013 Taylor Pursell Feb 6/Feb 13 2013

Due February 13, 2013

1. Alesha S: Regulation of DNA repair by parkin
   1. First oral presentation
   2. Wiki article -- first draft: CH391L/S2013 Alesha Stewart Feb 13 2013
2. Hala Ouzon: Linking RNA Polymerase Backtracking to Genome Instability in E. coli
   1. First oral presentation
   2. Wiki article -- first draft: Hala_Ouzon_Feb_13_2013
3. Taylor Pursell: Direct imaging of RecA nucleation and growth on single molecules of SSB-coated ssDNA.
   1. Second Oral Presentation
   2. Final Wiki Article: CH391L/S2013 Taylor Pursell Feb 13 2013
4. Tanya R: Recombination-restarted replication makes inverted chromosome fusions at inverted repeats
   1. Second Oral Presentation
   2. Final Wiki Article CH391L/S2013 Tanya Raymond Feb 13 2013

Due February 20, 2013

1. Logan M: The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.
   1. Wiki article -- first draft
2. Alesha S: Regulation of DNA repair by parkin
   1. Second oral presentation
   2. Wiki article -- final draft: CH391L/S2013 Alesha Stewart Feb 13 2013

Due February 27, 2013

1. Taylor P: Identification of Early Replicating Fragile Sites that Contribute to Genome Instability.
   1. Article:CH391L/S2013 Taylor Pursell Feb 27 2013
2. Tanya R: Atl1 regulates choice between global genome repair and transcription-coupled repair of O(6)-alkylguanines
   1. First Oral presentation
   2. CH391L/S2013 Tanya Raymond February 27 2013
3. Logan M: The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.
   1. Final Oral presentation
   2. CH391L/S2013 Logan Myler February 27 2013

Due March 20, 2013

1. Hala Ouzon: Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair [2]
   1. First oral presentation
   2. Wiki article -- first draft: CH391L/S2013 Hala Ouzon March 20 2013
2. Alesha S: Structure of a DNA glycosylase searching for lesions.
   1. First oral presentation
   2. Wiki article -- first draft: CH391L/S2013 Alesha Stewart Mar 20 2013
3. Taylor P: Identification of Early Replicating Fragile Sites that Contribute to Genome Instability.
   1. Final Article:CH391L/S2013 Taylor Pursell March 20 2013
4. Tanya R: Atl1 regulates choice between global genome repair and transcription-coupled repair of O(6)-alkylguanines
   1. Wiki article -- final draft: CH391L/S2013 Tanya Raymond Mar 20 2013

Due March 27, 2013

1. Logan M: Single-molecule imaging reveals target-search mechanisms during DNA mismatch repair.
   1. First Oral presentation
   2. First Draft -- CH391L/S2013 Logan Myler March 27 2013
2. Alesha S: Structure of a DNA glycosylase searching for lesions.
   1. Second oral presentation
   2. Wiki article -- Final draft: CH391L/S2013 Alesha Stewart Mar 27 2013
3. Hala Ouzon: Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair [3]
   1. First oral presentation
   2. Wiki article -- final draft: CH391L/S2013 Hala Ouzon March 20 2013

Due April 3, 2013

1. Taylor: Heteroplasmic mitochondrial DNA mutations in normal and tumour cells
   1. First Oral Presentation
   2. First Draft: CH391L/S2013 Taylor Pursell April 3 2013

Due April 10, 2013

1. Alesha S: p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression
   1. First oral presentation
   2. Wiki article -- first draft: CH391L/S2013 Alesha Stewart Apr 10 2013
2. Hala Ouzon: Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta [4]
   1. First oral presentation
   2. Wiki article -- first draft: CH391L/S2013 Hala Ouzon April 10 2013
3. Taylor: Heteroplasmic mitochondrial DNA mutations in normal and tumour cells
   1. Second Oral Presentation
   2. Final Draft: CH391L/S2013 Taylor Pursell April 10 2013
4. Tanya R: eRNAs are required for p53-dependent enhancer activity and gene transcription
   1. First oral presentation
   2. Wiki article CH391L/S2013 Tanya Raymond April 10 2013

Due April 17, 2013

1. Alesha S: p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression
   1. Second oral presentation
   2. Wiki article -- Final draft: CH391L/S2013 Alesha Stewart Apr 17 2013
2. Hala Ouzon: Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta [5]
   1. First oral presentation
   2. Wiki article -- final draft: CH391L/S2013 Hala Ouzon April 17 2013
3. Tanya R:
   1. Second oral presentation
   2. Final wiki draft CH391L/S2013 Tanya Raymond April 17 2013

Class Assignments

CH391L/S2013/SuggestedTopics

Suggested Reading

A Brief Overview of Cancer Biology

1. The hallmarks of cancer. Hanahan D, Weinberg RA. Cell. 2000 Jan 7;100(1):57-70.
2. Hallmarks of cancer: the next generation. Hanahan D, Weinberg RA. Cell. 2011 Mar 4;144(5):646-74.

DNA Double Strand Break (DSB) Repair

1. Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Niu H, Chung WH, Zhu Z, Kwon Y, Zhao W, Chi P, Prakash R, Seong C, Liu D, Lu L, Ira G, Sung P. Nature. 2010 Sep 2;467(7311):108-11.
2. Spontaneous DNA breakage in single living Escherichia coli cells. Pennington JM, Rosenberg SM. Nat Genet. 2007 Jun;39(6):797-802. Epub 2007 May 27.
3. Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells. Pierce AJ, Hu P, Han M, Ellis N, Jasin M. Genes Dev. 2001 Dec 15;15(24):3237-42.
4. Rad51 paralogues Rad55-Rad57 balance the antirecombinase Srs2 in Rad51 filament formation. Liu J, Renault L, Veaute X, Fabre F, Stahlberg H, Heyer WD. Nature. 2011 Oct 23;479(7372):245-8.
5. Purified human BRCA2 stimulates RAD51-mediated recombination. Jensen RB, Carreira A, Kowalczykowski SC. Nature. 2010 Oct 7;467(7316):678-83.
6. Direct imaging of RecA nucleation and growth on single molecules of SSB-coated ssDNA. Bell JC, Plank JL, Dombrowski CC, Kowalczykowski SC. Nature. 2012 Nov 8;491(7423):274-8.
7. Identification of a DNA nonhomologous end-joining complex in bacteria. Weller GR, Kysela B, Roy R, Tonkin LM, Scanlan E, Della M, Devine SK, Day JP, Wilkinson A, d'Adda di Fagagna F, Devine KM, Bowater RP, Jeggo PA, Jackson SP, Doherty AJ. Science. 2002 Sep 6;297(5587):1686-9.

DNA Replication and Genome Maintenance

1. Linking RNA polymerase backtracking to genome instability in E. coli. Dutta D, Shatalin K, Epshtein V, Gottesman ME, Nudler E. Cell. 2011 Aug 19;146(4):533-43.
2. Identification of Early Replicating Fragile Sites that Contribute to Genome Instability. Barlow JH, Faryabi RB, Callén E, Wong N, Malhowski A, Chen HT, Gutierrez-Cruz G, Sun HW, McKinnon P, Wright G, Casellas R, Robbiani DF, Staudt L, Fernandez-Capetillo O, Nussenzweig A. Cell. 2013 Jan 22. pii: S0092-8674(13)00008-1.
3. The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks. Hanada K, Budzowska M, Davies SL, van Drunen E, Onizawa H, Beverloo HB, Maas A, Essers J, Hickson ID, Kanaar R. Nat Struct Mol Biol. 2007 Nov;14(11):1096-104. Epub 2007 Oct 14.
4. Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae. Azvolinsky A, Giresi PG, Lieb JD, Zakian VA. Mol Cell. 2009 Jun 26;34(6):722-34.
5. Rep provides a second motor at the replisome to promote duplication of protein-bound DNA. Guy CP, Atkinson J, Gupta MK, Mahdi AA, Gwynn EJ, Rudolph CJ, Moon PB, van Knippenberg IC, Cadman CJ, Dillingham MS, Lloyd RG, McGlynn P. Mol Cell. 2009 Nov 25;36(4):654-66.

Replication and DNA Damage

1. Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae. Azvolinsky A, Giresi PG, Lieb JD, Zakian VA. Mol Cell. 2009 Jun 26;34(6):722-34.
2. Identification of Early Replicating Fragile Sites that Contribute to Genome Instability. Barlow JH, Faryabi RB, Callén E, Wong N, Malhowski A, Chen HT, Gutierrez-Cruz G, Sun HW, McKinnon P, Wright G, Casellas R, Robbiani DF, Staudt L, Fernandez-Capetillo O, Nussenzweig A. Cell. 2013 Jan 31;152(3):620-32.
3. Coordinated control of replication and transcription by a SAPK protects genomic integrity. Duch A, Felipe-Abrio I, Barroso S, Yaakov G, García-Rubio M, Aguilera A, de Nadal E, Posas F. Nature. 2013 Jan 3;493(7430):116-9.
4. Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions. Roberts SA, Sterling J, Thompson C, Harris S, Mav D, Shah R, Klimczak LJ, Kryukov GV, Malc E, Mieczkowski PA, Resnick MA, Gordenin DA. Mol Cell. 2012 May 25;46(4):424-35.
5. Topoisomerase I poisoning results in PARP-mediated replication fork reversal. Ray Chaudhuri A, Hashimoto Y, Herrador R, Neelsen KJ, Fachinetti D, Bermejo R, Cocito A, Costanzo V, Lopes M. Nat Struct Mol Biol. 2012 Mar 4;19(4):417-23.

DNA Mismatch Repair

1. Mispaired rNMPs in DNA are mutagenic and are targets of mismatch repair and RNases H. Shen Y, Koh KD, Weiss B, Storici F. Nat Struct Mol Biol. 2011 Dec 4;19(1):98-104.
2. Mismatch repair, but not heteroduplex rejection, is temporally coupled to DNA replication. Hombauer H, Srivatsan A, Putnam CD, Kolodner RD. Science. 2011 Dec 23;334(6063):1713-6.
3. Single-molecule imaging reveals target-search mechanisms during DNA mismatch repair. Gorman J, Wang F, Redding S, Plys AJ, Fazio T, Wind S, Alani EE, Greene EC. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):E3074-83.
4. Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair intermediates. Hombauer H, Campbell CS, Smith CE, Desai A, Kolodner RD. Cell. 2011 Nov 23;147(5):1040-53.
5. The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol η in response to oxidative DNA damage in human cells. Zlatanou A, Despras E, Braz-Petta T, Boubakour-Azzouz I, Pouvelle C, Stewart GS, Nakajima S, Yasui A, Ishchenko AA, Kannouche PL. Mol Cell. 2011 Aug 19;43(4):649-62.

DNA Inter-strand Crosslink Repair

1. BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair. Bunting SF, Callén E, Kozak ML, Kim JM, Wong N, López-Contreras AJ, Ludwig T, Baer R, Faryabi RB, Malhowski A, Chen HT, Fernandez-Capetillo O, D'Andrea A, Nussenzweig A. Mol Cell. 2012 Apr 27;46(2):125-35.
2. Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication. Shen X, Do H, Li Y, Chung WH, Tomasz M, de Winter JP, Xia B, Elledge SJ, Wang W, Li L. Mol Cell. 2009 Sep 11;35(5):716-23.

DNA Nucleotide Excision Repair

1. Structure of a DNA glycosylase searching for lesions. Banerjee A, Santos WL, Verdine GL. Science. 2006 Feb 24;311(5764):1153-7.

Class Participants

User:Ilya J. Finkelstein

User:Alesha Stewart

User:Tanya_E_Raymond

User:Hala Ouzon-Shubeita

User:Logan_R._Myler

User:Taylor Pursell