Premium
Swe1‐dependent and Swe1‐independent pathways controlling Hydroxyurea resistance in Saccharomyces cerevisiae
Author(s) -
tripathi kaushlendra,
Matmati Nabil,
Qin Tingting,
Zheng W. Jim,
mohanty Bidyt K,
Hannun Yusuf A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.591.2
Subject(s) - biology , chromatin , dna damage , saccharomyces cerevisiae , microbiology and biotechnology , dna replication , dna repair , g2 m dna damage checkpoint , chromatin remodeling , genetics , cell cycle checkpoint , cell cycle , gene , dna
Exposure to Hydroxyurea (HU) slows down or stalls DNA replication fork and activates the replication checkpoint. In Saccharomyces cerevisiae the replication fork component proteins Tof1, Csm3, Ctf4 and Mrc1 as well as its regulators such as Dcc1, Ctf18 and Ctf8 confer HU resistance. HU treatment of yeast cells causes actin depolarization in which several DNA integrity checkpoint proteins as well as morphogenesis controller Swe1 have been implicated. Recently we have shown that a sphingolipid gene ISC1 also controls cell morphology under HU stress by monitoring Swe1 and Cdk1 activity. Chromatin remodeling protein complexes such as Ino80 and Swr1 that function to reorganize histones during transcription and DNA repair, have recently been implicated in genotoxic tolerance in HU and methyl methanesulfonate (MMS). We have observed that although replication checkpoint proteins Mrc1, Tof1, Csm3 and Ctf4 and certain chromatin remodeling complex proteins such as Arp6 and Arp8 are involved in replication fork stalling, genotoxic tolerance and recovery from HU and MMS, their modes of action may be different. We find that they cooperate in HU/MMS sensitivity and recovery from HU/MMS. We have also observed that HU treatment causes morphological aberrations in strains lacking replication associated genes such as CTF4 and DCC1 . Interestingly, although HU causes morphological aberrations in the absence of ARP8 , an INO80 complex gene, it does cause any aberrations in the absence of ARP6 , a component of SWR1 complex gene. First time we are showing the functional interactions among replication checkpoint proteins, nuclear actin‐related proteins of chromatin remodelers, and actin regulators in the genotoxic tolerance and genotoxin‐induced cell morphology.