Ralph Scully
Beth Israel Deaconess Medical Center
Homologous recombinationDNA repairMolecular biologyGeneticsBiology
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Publications 86
#1Man-Li Luo (SYSU: Sun Yat-sen University)
#1Man-Li Luo (SYSU: Sun Yat-sen University)
Last. Xiao Zhen Zhou (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 36
view all 14 authors...
PARP inhibitor monotherapies effectively treat breast, ovary, prostate, and pancreatic cancer patients with BRCA1 mutations, but not the more frequent BRCA-wildtype cancers. Searching for strategies that would extend the use of PARP inhibitors to BRCA1-proficient tumors, we report here that the stability of BRCA1 protein following ionizing radiation (IR) is maintained by post-phosphorylational prolyl-isomerization adjacent to Ser1191 of BRCA1, which is catalyzed by prolyl-isomerase Pin1. Extinct...
#2Peter Bouwman (NKI-AVL: Netherlands Cancer Institute)H-Index: 19
Last. Lisa Wiesmüller (University of Ulm)H-Index: 22
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Since the identification and cloning of BRCA1 in 1994,1 and shortly thereafter of BRCA2 ,2 genetic tests of germline DNA to identify pathogenic variants in genes linked to hereditary breast and ovarian cancer (HBOC) have become mainstream.3 These tests are critical to identify women at increased risk relative to the general population. Women at moderate risk (2≤relative risk (RR) 4), including those with BRCA1 and BRCA2 pathogenic variants, may also benefit from preventive surgery. Germline muta...
#1Bernardo Rodriguez-Martin (University of Vigo)H-Index: 1
#2Eva G. Alvarez (University of Vigo)H-Index: 2
Last. Javier Temes (University of Santiago de Compostela)H-Index: 1
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About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear elem...
7 CitationsSource
#1Ralph Scully (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 38
#2Arvind Panday (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 7
Last. Nicholas A. Willis (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 12
view all 4 authors...
The major pathways of DNA double-strand break (DSB) repair are crucial for maintaining genomic stability. However, if deployed in an inappropriate cellular context, these same repair functions can mediate chromosome rearrangements that underlie various human diseases, ranging from developmental disorders to cancer. The two major mechanisms of DSB repair in mammalian cells are non-homologous end joining (NHEJ) and homologous recombination. In this Review, we consider DSB repair-pathway choice in ...
11 CitationsSource
#1Francesca MenghiH-Index: 9
#2Floris P BarthelH-Index: 10
Last. Edison T. LiuH-Index: 14
view all 12 authors...
Summary The tandem duplicator phenotype (TDP) is a genome-wide instability configuration primarily observed in breast, ovarian, and endometrial carcinomas. Here, we stratify TDP tumors by classifying their tandem duplications (TDs) into three span intervals, with modal values of 11 kb, 231 kb, and 1.7 Mb, respectively. TDPs with ∼11 kb TDs feature loss of TP53 and BRCA1 . TDPs with ∼231 kb and ∼1.7 Mb TDs associate with CCNE1 pathway activation and CDK12 disruptions, respectively. We demonstrate...
19 CitationsSource
#1Nicholas A. Willis (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 12
#2Arvind Panday (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 7
Last. Ralph Scully (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 38
view all 4 authors...
Classical non-homologous end joining (C-NHEJ) and homologous recombination (HR) compete to repair mammalian chromosomal double strand breaks (DSBs). However, C-NHEJ has no impact on HR induced by DNA nicking enzymes. In this case, the replication fork is thought to convert the DNA nick into a one-ended DSB, which lacks a readily available partner for C-NHEJ. Whether C-NHEJ competes with HR at a non-enzymatic mammalian replication fork barrier (RFB) remains unknown. We previously showed that cons...
3 CitationsSource
#1Francesca MenghiH-Index: 9
Last. Ed Liu
view all 10 authors...
#1Nicholas A. Willis (Harvard University)H-Index: 12
#2Richard L. Frock (HHMI: Howard Hughes Medical Institute)H-Index: 14
Last. Ralph Scully (Harvard University)H-Index: 38
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BRCA1, but not BRCA2, suppresses the formation of tandem duplications at stalled replication forks in primary mammalian cells.
21 CitationsSource
#1Sarmi Nath (IISc: Indian Institute of Science)H-Index: 1
#2Kumar Somyajit (IISc: Indian Institute of Science)H-Index: 13
Last. Ganesh Nagaraju (IISc: Indian Institute of Science)H-Index: 16
view all 5 authors...
The FANCJ DNA helicase is linked to hereditary breast and ovarian cancers as well as bone marrow failure disorder Fanconi anemia (FA). Although FANCJ has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), the molecular mechanism underlying the tumor suppressor functions of FANCJ remains obscure. Here, we demonstrate that FANCJ deficient human and hamster cells exhibit reduction in the overall gene conversions in response to a site-specific chromoso...
5 CitationsSource
#1Yung Hwang (UMMS: University of Massachusetts Medical School)H-Index: 2
#2Melinda Futran (UMMS: University of Massachusetts Medical School)H-Index: 1
Last. Merav Socolovsky (UMMS: University of Massachusetts Medical School)H-Index: 24
view all 8 authors...
Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase–dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors ar...
12 CitationsSource