STRUCTURE-FUNCTION STUDIES OF YEAST RNR1

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in de novo DNA synthesis and is allosterically controlled by relative levels of dNTPs to maintain a balanced pool of deoxynucleotide triphosphates (dNTPs) in the cell. In eukaryotes, the enzyme comprises a hetero-oligomer of a2 and b2 subunits. The a subunit (Rnr1) contains regulatory and catalytic sites; Rnr2, the b subunit, houses the diferric-tyrosyl radical crucial for catalysis. Tight control of dNTP pools is vital for cell viability; due to the crucial role RNR plays in balancing the relative levels of dNTPs, it is highly regulated transcriptionally, allosterically, by compartmentalization of the various subunits within the cell, and in S. cerevisiae by its protein inhibitor Sml1. The molecular basis for these processes is not fully understood. Crucial for rapidly dividing cells, RNR is a target for cancer therapy