Andre Nussenzweig, Ph.D.

NIH Distinguished Investigator

Laboratory of Genome Integrity

NCI/CCR

Research Topics

Genomic instability is a hallmark of cancer. Central to a cell's ability to maintain genomic stability are systems that monitor and repair DNA double strand breaks (DSBs). DSBs occur during normal DNA replication, in response to chemotherapeutic agents, and during physiological reactions including meiotic recombination in germ cells and antigen receptor rearrangements in lymphocytes. If not rapidly and faithfully repaired, DSBs can also be substrates for aberrant chromosomal translocations, which promote cancer. The focus of the Recombination Unit is to understand the mechanisms by which all cell types monitor and repair DSBs

Resources

Protocol for END-seq

An unbiased and genome-wide approach that maps DNA double-strand breaks (DSBs) with precision and sensitivity. END-seq provides a snapshot of DNA ends genome-wide, which can be utilized for understanding genome-editing specificities and the influence of chromatin on a variety of physiological and pathological processes.

END-seq: An Unbiased, High-Resolution, and Genome-Wide Approach to Map DNA Double-Strand Breaks and Resection in Human Cells

Wong N, John S, Nussenzweig A, Canela A. Methods Mol Biol. 2021;2153:9-31

https://pubmed.ncbi.nlm.nih.gov/32840769/

DNA Breaks and End Resection Measured Genome-wide by End Sequencing

Canela A, Sridharan S, Sciascia N, Tubbs A, Meltzer P, Sleckman BP, Nussenzweig A. Mol Cell. 2016; 63:898-911

https://pubmed.ncbi.nlm.nih.gov/27477910/

Protocol for SAR-seq

Synthesis Associated with Repair sequencing - a method to map sites of DNA repair synthesis by sequencing.

Neuronal enhancers are hotspots for DNA single-strand break repair

Wu, W, Hill, SE, Nathan, WJ, Paiano J, Callen E et. al. Nature. 2021; 593:440-444

https://pubmed.ncbi.nlm.nih.gov/33767446/

When the break is just around the loop

Genome Organization Drives Chromosome Fragility

Canela A, Maman Y, Jung S, Wong N, Callen E et. al. Cell. 2017;170:507-521

https://pubmed.ncbi.nlm.nih.gov/28735753

Inside the nucleus, DNA is packed in highly complex structures that help to control which genes are on and off each time. In this video abstract, we explain how this intricate architecture makes specific DNA sites more susceptible to breaks that, if not properly fixed, can lead to cancer.

Biography

Dr. Nussenzweig received his Ph.D. in Physics from Yale University in 1989. He completed his postdoctoral training in atomic physics in Paris with Dr. Serge Haroche, who was awarded the Nobel prize in Physics in 2012. Subsequently, Dr. Nussenzweig became a Research Fellow at Memorial Sloan-Kettering Cancer Center prior to joining the Experimental Immunology Branch as a tenure track investigator in 1998. Dr. Nussenzweig received tenure at NIH in 2003. In 2011, Dr. Nussenzweig established a new department at NCI called the Laboratory of Genome Integrity. Dr. Nussenzweig is an elected member of the European Molecular Biology Organization, a National Institutes of Health Distinguished Investigator and a 2019 inductee into the US National Academy of Medicine. In 2023, Dr. Nussenzweig was inducted into the American Academy of Arts and Sciences as well as the National Academy of Sciences.

Selected Publications

Canela A, Sridharan S, Sciascia N, Tubbs A, Meltzer P, Sleckman BP, Nussenzweig A. DNA Breaks and End Resection Measured Genome-wide by End Sequencing. Mol Cell. 2016;63(5):898-911.
Ray Chaudhuri A, Callen E, Ding X, Gogola E, Duarte AA, Lee JE, Wong N, Lafarga V, Calvo JA, Panzarino NJ, John S, Day A, Crespo AV, Shen B, Starnes LM, de Ruiter JR, Daniel JA, Konstantinopoulos PA, Cortez D, Cantor SB, Fernandez-Capetillo O, Ge K, Jonkers J, Rottenberg S, Sharan SK, Nussenzweig A. Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature. 2016;535(7612):382-7.
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. Identification of early replicating fragile sites that contribute to genome instability. Cell. 2013;152(3):620-32.
Bunting SF, Callén E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, Xu X, Deng CX, Finkel T, Nussenzweig M, Stark JM, Nussenzweig A. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell. 2010;141(2):243-54.
Callén E, Jankovic M, Difilippantonio S, Daniel JA, Chen HT, Celeste A, Pellegrini M, McBride K, Wangsa D, Bredemeyer AL, Sleckman BP, Ried T, Nussenzweig M, Nussenzweig A. ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell. 2007;130(1):63-75.