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PARPs and ADP-Ribosylation Come Into Focus
Molecular Cell
Editorial PARPs and ADP-Ribosylation Come Into Focus Not every field of biology has an identifiable provenance. Some fields slowly forge their way into existence over decades without a clear nucleating event, built from a diverse set of intriguing, yet unexplainable, observations that ultimately gel into a new focus area for research. Not so for the field of poly(ADP-ribosyl) transferases (PARPs) and ADP-ribosylation, which emerged quite rapidly from a series of related discoveries in the early 1960s. This field, which celebrated its 50th anniversary in 2013, is flourishing. And, perhaps surprisingly for such a mature field, it continues to yield novel observations that will provide important new biological insights into the foreseeable future. In recognition of the remarkable history and promising future of the field of PARPs and ADP-ribosylation, this special focus issue of Molecular Cell includes a collection of three Reviews (Bai, 947–958; Barkauskaite et al., 935–946; Bock et al., 959–969), three Perspectives (Daniels et al., 911–924; Knudsen et al., 925–934; Kraus, 902–910), and a SnapShot (Hottiger, 1134). Together, these pieces summarize the current state of the field, address some current controversies, and provide insights about what the future might hold. As I describe in the accompanying Perspective piece, the field of PARPs and ADP-ribosylation arose from studies on DNA-dependent RNA polymerase and a quest to reveal the mechanisms of RNA synthesis in vitro. What was, in essence, a wrong turn for the transcription field became a right turn for biomedical science. Today, the field of PARPs and ADP-ribosylation is experiencing a renaissance, with new methodologies driving new paths of research leading into unexpected areas of biology, as well as human health and medicine. In this regard, the U.S. Food and Drug Administration and the European Medicines Agency recently approved Olaparib, a PARP inhibitor, for use as a therapy against cancers deficient in homology-directed DNA repair. Over the past two decades, however, the field has moved away from its historical focus on PARP-1 and DNA repair. For example, current studies of PARPs in physiology are exploring the functions of other PARP family members in a diverse array of biological processes, such as metabolism, inflammation, signaling, and differentiation, while current studies of PARP inhibitors in cancer are examining effects on molecular endpoints other than DNA repair, such as the regulation of chromatin structure, gene expression, RNA stability, and protein folding. Given the broad expression patterns of PARP family members across tissue types, the range of biology for the family most certainly extends beyond the limited set of systems that we know now. More studies addressing the diverse biological (physiological and pathological) roles of PARPs are greatly needed. The field of PARPs and ADP-ribosylation has been garnering the attention of many different groups recently. This includes (1) scientists from outside the historical field, who have discovered that their favorite biological system requires one or more PARP family members or their favorite protein is modified by ADP-ribosylation; (2) clinicians with an interest in PARP inhibitors, who would like to learn more about the targets and mechanisms of action; and (3) organizations that host scientific conferences, such as Cold Spring Harbor Laboratory, which now sponsors a biennial meeting on PARPs and ADP-ribosylation (the second meeting in this series will be held in April 2016). The PARP- and ADP-ribosylation-themed pieces in this focus issue should have something for everyone. Newcomers can find an overview of the most exciting and current areas of research from leaders in the field, while experts can learn about the history of their field from scientists who were there at the beginning (see the interviews with Pierre Chambon and Masanao Miwa at the end of the accompanying Perspective). I hope the readers of Molecular Cell find these pieces interesting and informative for what they say about PARPs and ADP-ribosylation, as well as what they may suggest about other related areas of biology. Many thanks to all of the authors and reviewers who gave their time and energy to make this focus issue possible. ABOUT THE AUTHOR W. Lee Kraus is the Director of the Green Center for Reproductive Biology Sciences at UT Southwestern Medical Center, where he holds the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology Sciences. His lab studies the molecular mechanisms and functions of nuclear PARPs in gene regulation in research supported by the NIH/NIDDK. He is also the founding organizer of the Cold Spring Harbor Laboratory meeting on PARPs and ADP-ribosylation.
W. Lee Kraus Guest Editor http://dx.doi.org/10.1016/j.molcel.2015.06.014
Molecular Cell 58, June 18, 2015 ª2015 Elsevier Inc. 901
Editorial PARPs and ADP-Ribosylation Come Into Focus Not every field of biology has an identifiable provenance. Some fields slowly forge their way into existence over decades without a clear nucleating event, built from a diverse set of intriguing, yet unexplainable, observations that ultimately gel into a new focus area for research. Not so for the field of poly(ADP-ribosyl) transferases (PARPs) and ADP-ribosylation, which emerged quite rapidly from a series of related discoveries in the early 1960s. This field, which celebrated its 50th anniversary in 2013, is flourishing. And, perhaps surprisingly for such a mature field, it continues to yield novel observations that will provide important new biological insights into the foreseeable future. In recognition of the remarkable history and promising future of the field of PARPs and ADP-ribosylation, this special focus issue of Molecular Cell includes a collection of three Reviews (Bai, 947–958; Barkauskaite et al., 935–946; Bock et al., 959–969), three Perspectives (Daniels et al., 911–924; Knudsen et al., 925–934; Kraus, 902–910), and a SnapShot (Hottiger, 1134). Together, these pieces summarize the current state of the field, address some current controversies, and provide insights about what the future might hold. As I describe in the accompanying Perspective piece, the field of PARPs and ADP-ribosylation arose from studies on DNA-dependent RNA polymerase and a quest to reveal the mechanisms of RNA synthesis in vitro. What was, in essence, a wrong turn for the transcription field became a right turn for biomedical science. Today, the field of PARPs and ADP-ribosylation is experiencing a renaissance, with new methodologies driving new paths of research leading into unexpected areas of biology, as well as human health and medicine. In this regard, the U.S. Food and Drug Administration and the European Medicines Agency recently approved Olaparib, a PARP inhibitor, for use as a therapy against cancers deficient in homology-directed DNA repair. Over the past two decades, however, the field has moved away from its historical focus on PARP-1 and DNA repair. For example, current studies of PARPs in physiology are exploring the functions of other PARP family members in a diverse array of biological processes, such as metabolism, inflammation, signaling, and differentiation, while current studies of PARP inhibitors in cancer are examining effects on molecular endpoints other than DNA repair, such as the regulation of chromatin structure, gene expression, RNA stability, and protein folding. Given the broad expression patterns of PARP family members across tissue types, the range of biology for the family most certainly extends beyond the limited set of systems that we know now. More studies addressing the diverse biological (physiological and pathological) roles of PARPs are greatly needed. The field of PARPs and ADP-ribosylation has been garnering the attention of many different groups recently. This includes (1) scientists from outside the historical field, who have discovered that their favorite biological system requires one or more PARP family members or their favorite protein is modified by ADP-ribosylation; (2) clinicians with an interest in PARP inhibitors, who would like to learn more about the targets and mechanisms of action; and (3) organizations that host scientific conferences, such as Cold Spring Harbor Laboratory, which now sponsors a biennial meeting on PARPs and ADP-ribosylation (the second meeting in this series will be held in April 2016). The PARP- and ADP-ribosylation-themed pieces in this focus issue should have something for everyone. Newcomers can find an overview of the most exciting and current areas of research from leaders in the field, while experts can learn about the history of their field from scientists who were there at the beginning (see the interviews with Pierre Chambon and Masanao Miwa at the end of the accompanying Perspective). I hope the readers of Molecular Cell find these pieces interesting and informative for what they say about PARPs and ADP-ribosylation, as well as what they may suggest about other related areas of biology. Many thanks to all of the authors and reviewers who gave their time and energy to make this focus issue possible. ABOUT THE AUTHOR W. Lee Kraus is the Director of the Green Center for Reproductive Biology Sciences at UT Southwestern Medical Center, where he holds the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology Sciences. His lab studies the molecular mechanisms and functions of nuclear PARPs in gene regulation in research supported by the NIH/NIDDK. He is also the founding organizer of the Cold Spring Harbor Laboratory meeting on PARPs and ADP-ribosylation.
W. Lee Kraus Guest Editor http://dx.doi.org/10.1016/j.molcel.2015.06.014
Molecular Cell 58, June 18, 2015 ª2015 Elsevier Inc. 901