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Movies for human CST-Pola-primase bound to 3xTEL DNA template

ABSTRACT:

SUBMITTER: CI JI LIM

PROVIDER: EMPIAR-11358 | biostudies-other |

REPOSITORIES: biostudies-other

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Structures of the human CST-Polα-primase complex bound to telomere templates.

He Qixiang Q Lin Xiuhua X Chavez Bianca L BL Agrawal Sourav S Lusk Benjamin L BL Lim Ci Ji CJ

Nature 20220713 7924

The mammalian DNA polymerase-α-primase (Polα-primase) complex is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways<sup>1-4</sup> such as lagging-strand synthesis and telomere C-strand fill-in. The physical mechanism underlying how Polα-primase, alone or in partnership with accessory proteins, performs its complicated multistep primer synthesis function is unknown. Here we show that CST, a single-stranded DNA-binding accessory protein complex ...[more]

PMID: 35830881

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Structures of the human CST-Polα-primase complex bound to telomere templates.

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The structure of human CST reveals a decameric assembly bound to telomeric DNA.

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Project description:The CST-Polα/primase complex is essential for telomere maintenance and functions to counteract resection at double-strand breaks. We report a 4.6-Å resolution cryo-EM structure of human CST-Polα/primase, captured prior to catalysis in a recruitment state stabilized by chemical cross-linking. Our structure reveals an evolutionarily conserved interaction between the C-terminal domain of the catalytic POLA1 subunit and an N-terminal expansion in metazoan CTC1. Cross-linking mass spectrometry and negative-stain EM analysis provide insight into CST binding by the flexible POLA1 N-terminus. Finally, Coats plus syndrome disease mutations previously characterized to disrupt formation of the CST-Polα/primase complex map to protein-protein interfaces observed in the recruitment state. Together, our results shed light on the architecture and stoichiometry of the metazoan fill-in machinery.

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