PMID: 18728389Aug 30, 2008Paper

Mdt1/ASCIZ: a new DNA damage response protein family

Cell Cycle
Jörg Heierhorst

Abstract

DNA damage response pathways are crucial for genome stability and prevention of cancer and are overall remarkably conserved from yeast to mammals. Two novel DNA damage response proteins, yeast Mdt1 (Modifier of DNA damage tolerance 1) and human ASCIZ (ATM/ATR-substrate Chk2-interacting Zn(2+)-finger protein), were recently identified based on their interactions with the N-terminal FHA domains of the conserved checkpoint kinases Rad53 and Chk2, respectively, and ASCIZ was subsequently re-isolated as an ATM-interacting protein (ATMIN). Mdt1 and ASCIZ share remarkable sequence similarity (36% highly conserved residues, 17% identity) and extended SQ/TQ cluster domains (SCDs) typical of DNA damage response proteins. However, despite their structural similarities and conserved interactions with the checkpoint machinery, the two proteins seem to respond to different DNA lesions: the strongest phenotypes of ASCIZ deficiency are increased sensitivity to DNA base damaging agents and altered immunoglobulin gene diversification following enzyme-induced base damage in B lymphocytes, whereas absence of Mdt1 leads to hypersensitivity to 3'-blocked DNA double-strand breaks and inefficient recombinational maintenance of telomeres. The Mdt1/ASCI...Continue Reading

Citations

May 3, 2011·Cellular and Molecular Life Sciences : CMLS·Shahzad BhattiKum Kum Khanna
Feb 16, 2016·Scientific Reports·Katarzyna B LeszczynskaEster M Hammond
Oct 6, 2011·Biochemical and Biophysical Research Communications·Péter RapaliIgnacio Rodriguez-Crespo

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