Author
Roopesh Anand
Other affiliations: Francis Crick Institute, University of Zurich
Bio: Roopesh Anand is an academic researcher from University of Lugano. The author has contributed to research in topics: Homologous recombination & DNA repair. The author has an hindex of 13, co-authored 23 publications receiving 893 citations. Previous affiliations of Roopesh Anand include Francis Crick Institute & University of Zurich.
Topics: Homologous recombination, DNA repair, DNA, RAD51, DNA damage
Papers
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TL;DR: In this paper, the authors show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells.
263 citations
TL;DR: This work shows that CtIP is a co-factor of the MRE11 endonuclease activity within the MRN complex and defines the initial step of HR that is particularly relevant for the processing of DSBs bearing protein blocks.
228 citations
TL;DR: Findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAM HD1 promotes genome integrity.
135 citations
TL;DR: Recombinant Mlh1-Mlh3 complexes are produced and it is shown that it is an endonuclease that binds specifically Holliday junctions and represents a new paradigm for the function of the eukaryotic MutL protein family.
121 citations
TL;DR: It is reported that RECQL4 is an important participant in HR-dependent DSBR, which is the initial and an essential step of homologous recombination (HR)-dependent DNA double-strand break repair (DSBR).
72 citations
Cited by
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TL;DR: This Review discusses the most recent findings regarding the relative involvement of the different NHEJ proteins in the repair of various DNA-end configurations and the relevance of these different pathways to human disease.
Abstract: DNA double-strand breaks (DSBs) are the most dangerous type of DNA damage because they can result in the loss of large chromosomal regions. In all mammalian cells, DSBs that occur throughout the cell cycle are repaired predominantly by the non-homologous DNA end joining (NHEJ) pathway. Defects in NHEJ result in sensitivity to ionizing radiation and the ablation of lymphocytes. The NHEJ pathway utilizes proteins that recognize, resect, polymerize and ligate the DNA ends in a flexible manner. This flexibility permits NHEJ to function on a wide range of DNA-end configurations, with the resulting repaired DNA junctions often containing mutations. In this Review, we discuss the most recent findings regarding the relative involvement of the different NHEJ proteins in the repair of various DNA-end configurations. We also discuss the shunting of DNA-end repair to the auxiliary pathways of alternative end joining (a-EJ) or single-strand annealing (SSA) and the relevance of these different pathways to human disease.
1,061 citations
TL;DR: This Review considers DSB repair-pathway choice in somatic mammalian cells as a series of ‘decision trees’, and explores how defective pathway choice can lead to genomic instability.
Abstract: 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 somatic mammalian cells as a series of 'decision trees', and explore how defective pathway choice can lead to genomic instability. Stalled, collapsed or broken DNA replication forks present a distinctive challenge to the DSB repair system. Emerging evidence suggests that the 'rules' governing repair-pathway choice at stalled replication forks differ from those at replication-independent DSBs.
713 citations
Institute for Systems Biology1, University of Texas MD Anderson Cancer Center2, Mayo Clinic3, Massachusetts Institute of Technology4, Van Andel Institute5, University of Pennsylvania6, Baylor College of Medicine7, Texas A&M University8, University of Texas Health Science Center at Houston9, Washington University in St. Louis10, Buck Institute for Research on Aging11, University of California, San Francisco12, University of Texas at Austin13, University of Washington14
TL;DR: These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy and a new machine-learning-based classifier developed from gene expression data allowed to identify alterations that phenocopy deleterious TP53 mutations.
706 citations
TL;DR: This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotics recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase.
Abstract: The study of homologous recombination has its historical roots in meiosis. In this context, recombination occurs as a programmed event that culminates in the formation of crossovers, which are essential for accurate chromosome segregation and create new combinations of parental alleles. Thus, meiotic recombination underlies both the independent assortment of parental chromosomes and genetic linkage. This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotic recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase. A more in-depth review presents our understanding of how crossover and noncrossover pathways of meiotic recombination are differentiated and regulated. The final section of this review summarizes the studies that have defined defective recombination as a leading cause of pregnancy loss and congenital disease in humans.
627 citations
TL;DR: NHEJ is a single pathway with multiple enzymes at its disposal to repair DSBs, resulting in a diversity of repair outcomes, including many possible junctional outcomes from one DSB.
336 citations