{'fraction_non_alphanumeric': 0.041666666666666664, 'fraction_numerical': 0.009963768115942028, 'mean_word_length': 5.138888888888889, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
PARP-1 Activation—Bringing the Pieces Together

A model structure sheds light on how the PARP-1 protein is activated in DNA repair. The repair of DNA strand breaks is crucial for cell survival. In higher eukaryotes, cellular responses to DNA strand breaks are coordinated by a process called poly(ADP-ribosyl)ation (where ADP is adenosine diphosphate). This highly dynamic process begins with the hydrolysis of NAD+ (nicotinamide adenine dinucleotide) by poly(ADP-ribose) polymerases (PARPs), resulting in the polymerization of ADP-ribose moieties onto a substrate protein. The most active PARP in DNA damage recognition, PARP-1, is highly stimulated by single- and double-strand breaks (1). Because it is a clinically important molecular target in the treatment of several cancers, including breast and ovarian cancers (2), understanding how PARP-1 is activated after binding DNA strand breaks is an ongoing challenge. On page 728 of this issue, Langelier et al. (3) report key structural information about PARP-1 domain organization around a DNA double-strand break (DSB) that explains this activation.